Iranian Biomedical Journal
Year:2019 | Volume:23 | Issue:1|Papers Count:10

Dr. Younes Karimi was born in 1929 in Lotfabad Dargaz, Razavi Khorasan Province, where he accomplished the primary education. He received his diploma in Mashhad, northeast of Iran and followed his medical education and specialty in Infectious Diseases and Tropical Medicine at the University of Tehran by presenting his Ph. D. thesis entitled “ Dried smallpox vaccine" in 1975. He also attended microbiology and immunology courses at the Institute Pasteur of Paris. Returning to Iran, he was engaged at Pasteur Institute of Iran and devoted his scientific career for researching on infectious diseases and the control of these diseases in Iran. He was also the head of the Department of Epidemiology and the Deputy Director of Pasteur Institute of Iran[1]. He was a hard-working person with scientific prestige and dignified character and a man of action interested in the field activities...

Heterogeneous loss of function mutations at F8 and F9 genes causes X-linked recessive bleeding disorders, hemophilia A (HA) and hemophilia B (HB), respectively. HA is clinically indistinguishable from HB and accounts for more than 80% of hemophilia cases; the former affects 1/5000 and the latter 1/25000 male births worldwide. In Iran, it is estimated that around 4300 HA and 900 HB patients are under care. The standard care for hemophilia patients is lifelong on demand or prophylactic factor replacement therapy. However, the complications such as arthropathies in severe form of the disease and viral infections are not uncommon. The cost of prophylactic treatment is high and not affordable in developing countries. The annual cost of hemophilia treatment in Iran is not predictable, but it is estimated to be around 50, 000-60, 000 US dollars/patient...

Three-dimensional (3D) printing technology has revolutionized tissue engineering field because of its excellent potential of accurately positioning cell-laden constructs. One of the main challenges in the formation of functional engineered tissues is the lack of an efficient and extensive network of microvessels to support cell viability. By printing vascular cells and appropriate biomaterials, the 3D printing could closely mimic in vivo conditions to generate blood vessels. In vascular tissue engineering, many various approaches of 3D printing have been developed, including selective laser sintering and extrusion methods, etc. The 3D printing is going to be the integral part of tissue engineering approaches; in comparison with other scaffolding techniques, 3D printing has two major merits: automation and high cell density. Undoubtedly, the application of 3D printing in vascular tissue engineering will be extended if its resolution, printing speed, and available materials can be improved.

Background: Targeted co-delivery of siRNA and a chemotherapeutic drug is an attractive approach to cancer drug design and treatment. This study was carried out to design an anti-Mucin1 aptamer (Apt)-conjugated chitosan nanoparticle (NP) for targeted co-delivery of insulin-like growth factor receptor 1 (IGF-1R) Silencer siRNA and docetaxel (DTX) to SKBR3 cells. Methods: Characterization of nano-drugs, cellular uptake of NPs, cell viability, and gene expression studies were evaluated based on metastatic breast cancer cells. Results: The results of this study showed that NPs had spherical and smooth morphology with 110-118 nm in size and had positive zeta potential (12-14 mV). siRNA and DTX were considerably loaded into NPs. The appropriate conjugation of the Apt to the NPs was affirmed by gel electrophoresis. The Apt-conjugated NPs were observed to enhance the cellular uptake of NPs into the SKBR3 cells. Although the combination treatment significantly decreased the cell viability of SKBR3 cells, the augmentative effect was observed when Apt was conjugated to NPs. Furthermore, Apt-conjugated NPs dramatically reduced the genetic expression of IGF-1R, signal transducers and activators of transcription 3 (STAT3), matrix metalloproteinases (MMP9), and vascular growth factor (VEGF). Conclusion: The targeted NPs may augment the targeting of pathways involved in tumorigenesis and metastasis of breast cancer. Therefore, more animal model experiments are needed to further clarify the efficacy and safety of this functionalized nanodrug.

Background: Colorectal cancer (CRC) is one of the challenging types of cancers; thus, exploring effective biomarkers related to colorectal could lead to significant progresses toward the treatment of this disease. Methods: In the present study, CRC gene expression datasets have been reanalyzed. Mutual differentially expressed genes across 294 normal mucosa and adjacent tumoral samples were then utilized in order to build two independent transcriptional regulatory networks. By analyzing the networks topologically, genes with differential global connectivity related to cancer state were determined for which the potential transcriptional regulators including transcription factors were identified. Results: The majority of differentially connected genes (DCGs) were up-regulated in colorectal transcriptome experiments. Moreover, a number of these genes have been experimentally validated as cancer or CRC-associated genes. The DCGs, including GART, TGFB1, ITGA2, SLC16A5, SOX9, and MMP7, were investigated across 12 cancer types. Functional enrichment analysis followed by detailed data mining exhibited that these candidate genes could be related to CRC by mediating in metastatic cascade in addition to shared pathways with 12 cancer types by triggering the inflammatory events. Conclusion: Our study uncovered correlated alterations in gene expression related to CRC susceptibility and progression that the potent candidate biomarkers could provide a link to disease.

Background: ZFX is a transcriptional regulator in embryonic stem cells and plays an important role in pluripotency and self-renewal. ZFX is widely expressed in pluripotent stem cells and is down-regulated during differentiation of embryonic stem cells. ZFX has five different variants that encode three different protein isoforms. While several reports have determined the overexpression of ZFX in a variety of somatic cancers, the expression of ZFX-spliced variants in cancer cells is not well-understood. Methods: We investigated the expression of ZFX variants in a series of breast cancer tissues and cell lines using quantitative PCR. Results: The expression of ZFX variant 1/3 was higher in tumor tissue compared to marginal tissue. In contrast, the ZFX variant 5 was down-regulated in tumor tissues. While the ZFX variant 1/3 and ZFX variant 5 expression significantly increased in low-grade tumors, ZFX variant 4 was strongly expressed in high-grade tumors, demonstrating lymphatic invasion. In addition, our result revealed a significant association between the HER2 status and the expression of ZFX-spliced variants. Conclusion: Our data suggest that the expression of ZFX-spliced transcripts varies between different types of breast cancer and may contribute to their tumorigenesis process. Hence, ZFX-spliced transcripts could be considered as novel tumor markers with a probable value in diagnosis, prognosis, and therapy of breast cancer.

Introduction: Hepatitis C virus (HCV) is a blood-borne pathogen, resulting in liver cirrhosis and liver cancer. Despite of many efforts in development of treatments for HCV, no vaccine has been licensed yet. The purpose of this study was to design and prepare a specific mRNA, without 5' cap and poly (A) tail transcribed in vitro capable of coding core protein and also to determine its functionality. Methods: Candidate mRNA was prepared by in vitro transcription of the designed construct consisting of 5ʹ and 3ʹ untranslated regions of heat shock proteins 70 (hsp70) mRNA, T7 promoter, internal ribosome entry site (IRES) sequences of eIF4G related to human dendritic cells (DCs), and the Core gene of HCV. To design the modified mRNA, the 5' cap and poly (A) tail structures were not considered. DCs were transfected by in vitro-transcribed messenger RNA (IVT-mRNA) and the expressions of green fluorescent protein (GFP), and Core genes were determined by microscopic examination and Western blotting assay. Results: Cell transfection results showed that despite the absence of 5' cap and poly (A) tail, the structure of the mRNA was stable. Moreover, the successful expressions of GFP and Core genes were achieved. Conclusion: Our findings indicated the effectiveness of a designed IVT-mRNA harboring the Core gene of HCV in transfecting and expressing the antigens in DCs. Considering the simple and efficient protocol for the preparation of this IVT-mRNA and its effectiveness in expressing the gene that it carries, this IVT-mRNA could be suitable for development of an RNA vaccine against HCV.

Background: Type 2 diabetes mellitus (T2DM) is related to the gut microbiota with numerous molecular mechanisms. Modulating the gut microbiota by probiotics could be effective in management of T2DM. The aim of the present trial was to evaluate the effect of Lactobacillus casei on glycemic control and serum sirtuin1 (SIRT1) and fetuin-A in patients with T2DM. Methods: Forty patients with T2DM (n = 20 for each group) were divided into intervention (probiotic) and placebo groups. The intervention group received a daily capsule containing 108 cfu of L. casei for eight weeks. The patients in placebo group took capsules containing maltodextrin for the same time duration. Anthropometric measurements, dietary intake questionnaires, and blood samples were collected, and the patients were assessed by an endocrinologist at the beginning and at the end of the trial. Results: Fasting blood sugar, insulin concentration, and insulin resistance significantly decreased in probiotic group compared with placebo group (-28. 32 [-50. 23 to-6. 41], 0. 013;-3. 12 [-5. 90 to-0. 35], 0. 028;-32. 31 [-55. 09 to-9. 54], 0. 007, respectively). Moreover, HbA1c reduced after intervention, but the reduction was not significant (-0. 45 [-0. 96 to 0. 05], 0. 077). In comparison with placebo, the L. casei supplementation significantly increased SIRT1 and decreased fetuin-A levels at the end of the trial (0. 52 [0. 026 to 1. 02], 0. 040;-17. 56 [-32. 54 to-2. 58], 0. 023, respectively). Conclusion: L. casei supplementation affected SIRT1 and fetuin-A levels in a way that improved glycemic response in subjects with T2DM. Affecting the SIRT1 and fetuin-A levels introduces a new known mechanism of probiotic action in diabetes management.

Background: This study was undertaken to analyze if different preparation and exposure periods of eluates from ocular prosthesis acrylic resin influence the cytotoxicity for conjunctival cells. Methods: Twenty-four acrylic resin specimens were divided, according to the period of eluate exposure to Chang conjunctival cells (24 and 72 hours). Eluates were prepared in four different ways: 24, 48, and 72 hours of resin specimen immersion in medium and 24 hours of immersion in water, followed by 24 hours of immersion in medium. MTT assay was used to evaluate the cytotoxic effect. The production of IL-1β , IL-6, TNF-α , and chemokine macrophage inflammatory protein 1α was evaluated by ELISA, while the mRNA expression of type IV collagen (COL IV), transforming growth factor β (TGF-β ), and matrix metalloproteinase 9 (MMP9) were evaluated by real-time RT-PCR technique. The statistical analysis was carried out using ANOVA with Bonferroni post-hoc test and the student’ s t-test (p < 0. 05). Results: Significant quantities of IL-6 (4. 594 pg/mL) and mRNA expression of COL IV (1. 58) were verified at 72 hours of eluate exposure to cells, as compared to 24 hours. After the 72-hour exposure of eluates to cells, lower cell proliferation (88. 4%) and higher IL-6 quantities (12. 374 pg/mL), as well as mRNA expression of COL IV (2. 21), TGF-β (2. 02), and MMP9 (5. 75) were observed, which corresponded to 72 hours of a specimen immersed in medium. Conclusion: Longer periods of eluate preparation and exposure from the acrylic resin to cells are related to higher production of proinflammatory cytokines and extracellular matrix proteins.

Background: Aberrant activation of phosphatidylinositol-3 kinases (PI3K)/AKT/mTOR (mammalian target of rapamycin) pathway is a critical event during gastric cancer progression. Selective function of AKT inhibitor AZD5363 in PI3KCA mutant gastric cancer necessitates the assessment of PI3KCA mutations in these patients. Methods: The study included 100 patients with gastric cancer who underwent surgical resection at Imam Reza Hospital, Tehran, Iran, between January 2009 and December 2016. Mutations in codon 1047 of PIK3CA were evaluated by tetra-primer ARMS-PCR and direct sequencing methods. Results: We detected p. H1047R and p. H1047L in eight and three samples, respectively. Also, a significant association was found between PIK3CA mutations and lymphatic invasion. Kaplan-Meier analysis demonstrated no significant differences in overall survival between patients with and without mutations. Conclusion: Our study detected gain-of-function mutations in exon 20 of PI3KCA gene in 11% of gastric cancer patients. Future studies are needed to assess the mutation rate in other regions of this gene to find eligible patients for targeted therapies.