Transcriptional regulation of E-cadherin and oncoprotein E7 by valproic acid in HPV positive cell lines

Objective(s): Valproic acid (VPA) has proven to be as one of the most promising useful drug with anticancer properties. In this study, we investigate the VPA effects on E-cadherin expression in HeLa, TC1, MKN45, and HCT116 cell lines. This study assesses the effects of VPA on human papillomavirus E7 expression in HPV positive cell lines. Materials and Methods: Cell lines were treated by 2 mmol/l VPA and expression of E-cadherin and E7 was analyzed by quantitative real-time PCR. Student�s t test and ANOVA were used to determine changes in expression levels. Results: The results revealed that mean of E-cadherin expression is increased by VPA 1.8 times in HCT116 and MKN45 cell lines, also the mean of E-cadherin mRNA levels is up-regulated 2.9 times in HeLa and TC1 cell lines. So, E-cadherin augmentation induced by VPA in HeLa and TC-1, HPV positive cell lines, is higher than HPV negative cell lines MKN45 and HCT116. The mean of HPV E7 expression is decreased by VPA, 4.6 times in in HeLa and TC-1 cell lines. Conclusion: This study demonstrates that re-expression of E-cadherin by VPA in HPV positive cell lines is more than HPV negative cell lines. Whereas, HPV E7 reduces the expression of E-cadherin, reduction of HPV E7 expression by VPA is related to more augmentation of E-cadherin in HPV positive cell lines. So, this study demonstrates that VPA has more anticancer properties in HPV positive cell lines, and could potentially be a promising candidate for cervical cancer treatment. © 2016, Mashhad University of Medical Sciences. All rights reserved

The role of MicroRNA signature as diagnostic biomarkers in different clinical stages of colorectal cancer

Objective: Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer-related death worldwide. The early diagnosis of colorectal tumors is one of the most important challenges in cancer management. MicroRNAs (miRNAs) have provided new insight into CRC development and have been suggested as reliable and stable biomarkers for diagnosis and prognosis. The aim of this study was to analyze the differential expression of miRNAs at different stages of CRC searching for possible correlation with clinicopathological features to examine their potential value as diagnostic biomarkers. Materials and Methods: In this case-control study, plasma and matched tissue samples were collected from 74 CRC patients at stage II-IV as well as blood samples from 32 healthy controls. After exhaustive study of the current literature, eight miRNAs including miR-200c, 20a, 21, 31,135b, 133b,145 and let-7g were selected. The expression level of the miRNAs was assayed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Statistical analysis, including t test , Mann-Whitney U, Kruskall-Wallis tests and receiver operating characteristic (ROC) curve was applied, where needed. Results: Significantly elevated levels of miR-21, miR-31, miR-20a, miR-135b, and decreased levels of miR-200c, miR-145 and let-7 g were detected in both plasma and matched tissue samples compared to the healthy group (P0.05). ROC for tissue miRNAs showed an area under the ROC curve (AUC) of 0.98 and P<0.001 for miR-21, 0.91 and P<0.001 for miR-135b, 0.91 and P<0.001 for miR-31, and 0.92 and P<0.001 for miR-20a. Conclusion: Our results indicate that the expression levels of microRNAs are systematically altered in CRC tissue and plasma. In conclusion, detection of miR-21, miR-135b, miR-31 and miR-20a levels in the tissue might be helpful to illuminate the molecular mechanisms underlying CRC carcinogenesis and serve as tumor-associated biomarkers for diagnosis. © 2018 Royan Institute (ACECR). All Rights Reserved

Identification of Azole Resistance Markers in Clinical Isolates of Candida tropicalis Using cDNA-AFLP Method

Background: Global reports have highlighted the increasing prevalence of Candida tropicalis infections as well as organism's drug resistance. This study aimed at identifying azole resistance markers in clinical isolates of C. tropicalis, which will be a great resource for developing new drugs. Methods: Two susceptible and resistant isolates of C. tropicalis were recovered from an epidemiological investigation of candidiasis in immunocompromised patients. C. tropicalis ATCC 750 was used as reference strain. Antifungal susceptibility to fluconazole and itraconazole was determined using Clinical and Laboratory Standards Institute (CLSI) method. Complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) technology and real-time reverse-transcriptase (RT) PCR were used for identification of potential genes involved in azole resistance of C. tropicalis clinical isolates. Results: Five genes encoding the following enzymes were identified as superoxide dismutase (SOD) implicated in antioxidant defense, ornithine aminotransferase (OAT), acetyl ornithine aminotransferase (ACOAT), adenosylmethionine-8-amino-7-oxononanoate aminotransferase (DAPA AT), and 4-aminobutyrate aminotransferase (ABAT)-belonging to pyridoxal phosphate (PLP) dependent enzymes and acting in an important physiological role in many fungal-cell cycles. Real-time RT-PCR confirmed mRNA level of the aforementioned genes. Conclusion: Our findings showed that factors such as PLP-dependent enzymes and SOD might be implicated in drug resistance in C. tropicalis clinical isolate. Therefore, further studies are required to explore the accurate biological functions of the mentioned genes that would be helpful for effective drug development. © 2016 Wiley Periodicals, Inc

The interplay between EBV and KSHV viral products and NF-κB pathway in oncogenesis

Among the DNA tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV), account for a considerable percentage of virus-associated cancers. Deregulation of transcription factors signaling pathways is one of the most significant oncogenic characteristics of EBV and KSHV. NF-κB is a transcription factor that play a remarkable role in oncogenesis because of its function as a master regulator of a spectrum of genes involved in physiological and pathophysiological process. Constitutive activation of NF-κB is a frequent and well-described event in many human malignancies. Compelling evidence represent EBV and KSHV are capable of targeting different components of NF-κB cascade. Here, we summarized recent findings to clarify the precise relationship between dysregulation of NF-κB and EBV and KSHV-related malignancies. This essay also emphasizes on contribution of various viral products in developing cancer through alteration of NF-κB signaling pathway. © 2020, The Author(s)

The role of viruses in adenocarcinoma development

Cancer is a leading public health issue that accounts for million deaths around the world every year. Human cancers contain over 100 types, which are categorized into different groups. Adenocarcinoma is one of those categories of cancer that begins from the glans and involves various tissues such as lung, esophagus, pancreas, prostate and colorectal. A range of risk factors has been identified for the development and progression of adenocarcinomas. One of these risk factors are viruses that serves special mechanisms to affect important host cell factors and tumorigenic pathways, contributing in development and promotion of adenocarcinomas. Here, we summarized the main viruses and their mechanisms implicated in the course of various adenocarcinomas development. © 2020 Elsevier B.V

Molecular epidemiology of human respiratory syncytial virus in Iranian children less than 5 years in 2007: a study on 72 cases

&quot;n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Human respiratory syncytial virus (HRSV) is the most important viral agent of acute lower respiratory tract disease in infants and young children worldwide. This virus is responsible for 50% brochiolitis and 25% pneumonia in infants. There are limited data of molecular epidemiology of HRSV from developing countries. This is the report on the molecular epidemiology of human respiratory syncytial virus in Iran.&quot;n&quot;nMethods: In this study, RT-PCR for second hypervariable region of the HRSV G glycoprotein was performed on 72 throat swabs collected from children less than 5 years of age with acute respiratory symptoms in 1386.&quot;n&quot;nResults: Of the 72 throat swabs collected from children with acute respiratory symptoms, 14 (19.44%) were positive for HRSV. Phylogenetic analysis revealed that all HRSV-positive samples clustered in three genotypes of subgroup A: 12 strains (85/71%) in genotype GA2, 1 strain (7/1%) in genotype GA1, and 1 strain (7/1%) in genotype GA5. In this study we couldn&apos;t identify any genotype of subgroup B.&quot;n&quot;nConclusion: Our results revealed that multiple genotypes of subgroup A were co-circulated during 1386 in children less than 5 years of age in Iran. Also this study revealed that genotype GA2 was predominant genotype in isolates were obtained from several cities (Tehran, Isfahan, Karaj, Qazvin, Bandar Abbas, Shahreza), so we speculate that this genotype may be predominant during 1386 in Iran. This study supported that RT-PCR for second variable region of G protein is an effective method for further studies of HRSV genotype designation in Iran

Detection of extensively drug-resistant and hypervirulent Klebsiella pneumoniae ST15, ST147, ST377 and ST442 in Iran

In this study, we focused on the emergence of extensively drug-resistant (XDR), pandrug-resistant (PDR), and hypervirulent Klebsiella pneumoniae (hvKP) in Iran. During 2018 to 2020 a total of 52 K. pneumoniae isolates were collected from different clinical specimens. The hvKP isolates were identified by PCR amplification of virulence and capsular serotype-specific genes. Hypermucoviscous K. pneumoniae (hmKP) were identified by string test. Carbapenem-resistant hvKP (CR-hvKP), multidrug-resistant hvKP (MDR-hvKP), extensively drug-resistant hvKP (XDR-hvKP), and pandrug-resistant hvKP (PDR-hvKP) were determined by disc diffusion method, Carba-NP test and PCR method. XDR-hvKP isolates were typed by multilocus sequence typing (MLST). Among all K. pneumoniae isolates 14 (26.9) were identified as hvKP and 78.6 (11/14) of them were hmKP however, none of the classic K. pneumoniae (cKP) isolates were hmKP. The predominant capsular serotype of hvKP was K2 (42.85) followed by K1 (35.71). The prevalence of MDR-hvKP, XDR-hvKP and PDR-hvKP isolates were 6 (42.9), 5 (35.7) and 1 (7.1), respectively. ESBL production was found in 85.7 of hvKP isolates and most of them carried bla TEM gene (78.6) and 6 isolates (42.9) were CR-hvKP. Among hvKP isolates, 1 (7.1), 2 (14.3), 3 (21.4), 8 (28.6), and 11 (78.6) carried bla NDM-6, bla OXA-48, bla CTX-M, bla SHV, and bla TEM genes, respectively. According to MLST analysis, 2, 1, 1, and 1 XDR-hvKP isolates belonged to ST15, ST377, ST442, and ST147, respectively. The occurrence of such isolates is deeply concerning due to the combination of hypervirulence and extensively drug-resistance or pandrug-resistance. © 2021 Akadémiai Kiadó, Budapest