Akram Siavoshi; Mahdieh Taghizadeh; Elahe Dookhe; Mehran Piran; Mahsa Saliani; Shahla Mohammad Ganji
Abstract
Epithelial ovarian cancer (EOC), as a challenging disease among women with poor prognosis and unclear molecular pathogenesis, each year is responsible for 140000 deaths globally. Recent progress in the field revealed the importance of proteins as key players of different biological ...
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Epithelial ovarian cancer (EOC), as a challenging disease among women with poor prognosis and unclear molecular pathogenesis, each year is responsible for 140000 deaths globally. Recent progress in the field revealed the importance of proteins as key players of different biological events. Considering the complicated protein interactions, taking a deeper look at protein-protein interactions (PPIs) could be considered as a superior strategy to unravel complex mechanisms encountered with regulatory cell signaling pathways of ovarian cancer. Hence, PPI network analysis was performed on differentially expressed genes (DEGs) of ovarian cancer to discover hub genes which have the potential to be introduced as biomarkers with clinical utility. A PPI network with 600 DEGs was constructed. Network topology analysis determined UBC, FN1, SPP1, ACTB, GAPDH, JUN, and RPL13A, with the highest Degree (K) and betweenness centrality (BC), as shortcuts of the network. KEGG pathway analysis showed that these genes are commonly enriched in ribosome and ECM-receptor interaction pathways. These pivotal hub genes, mainly UBC, FN1, RPL13A, SPP1, and JUN have been reported previously as potential prognostic biomarkers of different types of cancer. However, further experimental molecular studies and computational processes are required to confirm the function and association of the identified hub genes with epithelial ovarian cancer prognosis.
Mina Jahandideh; Ebrahim Barzegari
Abstract
MicroRNAs are interesting as cancer diagnostic and prognostic biomarkers because of their unique tissue expression profiles, higher stability in the blood in comparison to mRNAs, and the possibility for reliable quantification. In the case of prostate cancer (PCa), it is currently ...
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MicroRNAs are interesting as cancer diagnostic and prognostic biomarkers because of their unique tissue expression profiles, higher stability in the blood in comparison to mRNAs, and the possibility for reliable quantification. In the case of prostate cancer (PCa), it is currently emphasized to explore new biomarkers, particularly from microRNAs which are freely available in the bloodstream. In this study, the gene expression omnibus database (GEO), a repository of microarray data for PCa circulating extracellular vesicle-free microRNAs profiling, was analyzed for differentially expressed miRNAs (DE-miRs). Top 20 most differentially expressed miRs with significant (adjusted p-value < 0.01) high expression (fold change) levels were extracted by the simultaneous application of different filtering criteria. Then, microRNA-gene networks were constructed for the two sets of positively (n=20) or negatively (n=20) regulated miRNAs. Gene ontology annotations of the target gene sets were also extracted and analyzed. Results indicated that human miR-1587, miR-223-3p, miR-3125, and miR-642b-3p are highly significant DE-miRs in PCa. In addition, human miR-4459, miR-1273g, miR 642a-3p, and miR-642b-3p were identified as top-ranked hubs in the relevant miRNA-gene networks. FOXK1, PML, CD24, ATN1, BAZ2A, CDKN1A, NUFIP2, and HARNPU were identified as microRNA target genes with significant dysregulation. miR-4459, miR-1273g-3p, miR-3135b, miR-5001-5p, and miR-1587 were proposed as novel microRNAs with the potential to be utilized as diagnostic biomarkers of prostate cancer among circulating vesicle-free miRNAs.
Masoud Sattari; Mehdi Bibak; Shima Bakhshalizadeh; Mohammad Forouhar Vajargah
Abstract
The Caspian Sea is the largest inland body of water in the world and so has both common characteristics of seas and lakes with over 153 fish species which inhabit the sea and its basin. However, little is known about the trace element (TE) contaminations (TECs) in its tissues. In ...
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The Caspian Sea is the largest inland body of water in the world and so has both common characteristics of seas and lakes with over 153 fish species which inhabit the sea and its basin. However, little is known about the trace element (TE) contaminations (TECs) in its tissues. In the present study, 122 specimens of three fish species including Rutilus caspius (Roach, n=71), Leuciscus aspius (Asp, n=20), and Tinca tinca (Tench, n=31) were collected from three different fisheries regions (i.e. Astara, Anzali and Kiashahr) of the southern part of the Caspian Sea from September 2017 to June 2018. Inductively coupled plasma optical emission spectrometry (ICP-OES) was employed to measure TE levels in different fish tissues. An attempt was made to assess possible influences of habitat on element accumulation in the liver and kidney of three fish species in the southwest of the Caspian Sea basin. Some elements including Ca, K, Mg, P, S, Sc, and Sr showed different concentrations in the liver and kidney. Also their levels were significantly different between freshwater resident (Tench) and marine (Roach) species (p < 0.05). The differences among TECs in the liver and kidney of Roach, Asp and Tench were reduced to three components using principal component analysis (PCA). Results indicated that 83.60% of the total variability is related to TEs such as Cu, Fe, Sr, Ca, S, Na, Mg, K, and Al. The impact of habitat variability on the element accumulation was confirmed through linear chart obtained for liver and kidney (as body filtering organs) of Roach and Asp as marine residents as well as Tench as a freshwater resident. This could illustrate the borderline created by these habitats.
Nazanin Mardokh Rohani; Mohammad Khalaj-Kondari; Majid Khodayi-Shahrak; Mahnaz Talebi; Mohammad Ali Hoseinpur Feizi
Abstract
Recent genome-wide association studies have introduced several genetic variants which contribute to the late-onset Alzheimer's disease (LOAD). Polymorphisms of CHAT, TOMM40, and SORL1 genes have been reported to be associated with the LOAD phenotype. This study was endeavored to evaluate ...
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Recent genome-wide association studies have introduced several genetic variants which contribute to the late-onset Alzheimer's disease (LOAD). Polymorphisms of CHAT, TOMM40, and SORL1 genes have been reported to be associated with the LOAD phenotype. This study was endeavored to evaluate the association of the CHAT rs3810950, TOMM40 rs1160985 and SORL1 rs11218304 polymorphisms with the LOAD in the Turkish-speaking Azeri population of northwest Iran. In a case-control study, we included 174 cases: 88 cases with LOAD diagnosis and 86 healthy individuals. Peripheral blood samples were collected and the genomic DNA of all participants were extracted. Genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. We did not observe any significant association between the CHAT rs3810950 and SORL1 rs11218304 alleles with the LOAD. However, both the TOMM40 rs1160985 minor allele T and TT genotype showed significant negative associations with the LOAD. Hence, the TOMM40 rs1160985 polymorphism could be considered as a protective genetic factor against the LOAD in the Turkish-speaking Azeri population of northwest Iran.
Azadeh Haghighitalab; Maryam M. Matin; Fatemeh Khakrah; Ahmad Asoodeh; Ahmad Reza Bahrami
Abstract
Despite the prominent therapeutic potentials of stem cells, their use in cell therapy has been challenged with some unreproducible and inconsistent outcomes in addition to the risk of rejection and tumorigenesis. Gaining novel insights to the importance of the conditioned medium, ...
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Despite the prominent therapeutic potentials of stem cells, their use in cell therapy has been challenged with some unreproducible and inconsistent outcomes in addition to the risk of rejection and tumorigenesis. Gaining novel insights to the importance of the conditioned medium, secretory factors and extracellular vesicles as the functional components of the cultured stem cells, suggested the idea of substituting the cells with their cell-free counterparts. Biological properties of these products are influenced by the cues received from their microenvironment. Hence, providing optimal and fully defined culture conditions is essential for their preparation. Fetal bovine serum (FBS), one of the most routine supplements of cell culture, is enriched by endogenous extracellular vesicles (EVs). These EVs will affect the yield, purity and functional features of the cell-free products. Here, we endeavored to examine and compare three different methods including ultrasonication, ultrafiltration and polymer-based precipitation, to deplete EVs from FBS. We chose easy to perform and fast methods with the capacity for high-throughput applications. Based on our observations, although all examined methods were able to deplete EVs from FBS to some extent, polymer-based precipitation could be considered as the method of choice with minimal consequences on the biological requirements of FBS to support cell growth and characteristics. Due to similarities between FBS and some other biological solutions, this strategy would be suitable for EV-depletion from other liquids with high concentrations of proteins and nutrients. Moreover, it could be applied for preparation of optimal culture conditions for nanoparticle applications.
Zohreh Sohrabi Nezhad; Hassan Marashi; Nasrin Moshtaghi
Abstract
Silver nanoparticles are widely used in manufacturing of different products considering their unique physical and chemical properties. Also they have been noticed in medical diagnosis and treatment because of their antibacterial properties. Physical and chemical methods of producing ...
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Silver nanoparticles are widely used in manufacturing of different products considering their unique physical and chemical properties. Also they have been noticed in medical diagnosis and treatment because of their antibacterial properties. Physical and chemical methods of producing nanoparticles, are expensive and are not safe enough as toxic substances may remain in the final preparations. To solve this problem, biological production of nanoparticles is considered as an efficient alternative method. In present study, synthesis of silver nanoparticles via seeds, petals, roots, and hairy root extracts of Calendula officinalis were performed. These nanoparticles were characterized by means of spectrophotometer, particle size analyzer and transmission electron microscope. Nanoparticles which were synthesized by hairy root extract showed the highest absorption at 430 nm (1/6 a.u) and the smallest size (5/3 nm), in comparison to other examined particles. Results confirmed the better performance of hairy root extracts in the synthesis of silver nanoparticles.
Parisa Farrokh; Fatemeh Salimi
Abstract
Thermostable proteases are one of the pivotal enzymatic groups which play fundamental roles in biotechnologyrelated industries. The identification of bacterial thermostable enzymes through screening programs is a time and cost consuming process. So, extensive bioinformatics and experimental ...
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Thermostable proteases are one of the pivotal enzymatic groups which play fundamental roles in biotechnologyrelated industries. The identification of bacterial thermostable enzymes through screening programs is a time and cost consuming process. So, extensive bioinformatics and experimental studies have been conducted to reveal thermo stabilizing factors. The current study was aimed to evaluate distinctive indicators among 33 thermostable and 10 mesostable proteolytic enzymes. The frequency of individual amino acids, aliphatic indexes, melting temperatures, isoelectric points, as well as, the frequency of AXXXA and GXXXG motifs were determined and compared among these enzymes. In addition, types of proteolytic enzymes and their active sites were assigned. Moreover, the frequency of alpha helixes, polar surface regions, and packing volumes of these enzymes with the known structures were characterized. Results showed that the frequency of Ala and AXXXA motifs were significantly higher in thermostable proteolytic enzymes, while they possess lower contents of Met, His, Lys and Leu in comparison to mesostable enzymes (P<0.05). According to statistical analysis, thermostable proteolytic enzymes indicated meaningful lower packing volumes than mesostable enzymes (P<0.05). Findings of the current study in addition to more detailed investigations on the thermostability mechanisms of various protein families are essential for designing more efficient industrial enzymes with functional properties at high temperatures.
Roghaye Lorestani; Sohrab Boozarpour; Sakineh Alijanpour; Leila Ahangar
Abstract
Schizophrenia is an irritating mental disorder that affects around 1% of the world's population. The immune system contributes to the onset of the disease, particularly through production and secretion of some cytokines. In patients with schizophrenia, the balance of Th1 to Th2 ratio ...
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Schizophrenia is an irritating mental disorder that affects around 1% of the world's population. The immune system contributes to the onset of the disease, particularly through production and secretion of some cytokines. In patients with schizophrenia, the balance of Th1 to Th2 ratio is often altered. In the present study, we investigated these changes by measuring the gene expression levels of IFN-γ and T-bet as Th1 indicators, as well as IL-4 and GATA-3 as representatives for Th2. Blood samples of schizophrenic patients (n=25) and healthy individuals (n=10) were obtained. Total RNA was extracted from leukocytes and cDNA synthesis was performed based on provided protocols. Real-time PCR technique was utilized for the assessment of gene expression levels. Results indicated a significant increase in the expression of IFN-γ and its transcription factor, T-bet, while IL-4 gene expression was reduced significantly. The expression level of GATA-3 gene revealed no meaningful changes. Altogether, results confirmed the relative shift of Th1 to Th2 status in the patient with schizophrenia and re-emphasize the importance of the inflammatory events in the incidence of the disease. Moreover, a new index was introduced based on the IFN-γ and T-bet genes expression, which can determine healthy condition with total accuracy of 79%.
Sepideh sadat Hosseini; Shadi Mehrzad; Halimeh Hassanzadeh; Hamid Reza Bidkhori; Mahdi Mirahmadi; Madjid Momeni-Moghaddam; Fatemeh Sadeghifar; Moein Farshchian
Abstract
Mesenchymal stem/stromal cells (MSCs) as one of the most important types of adult stem cells secrete a variety of immunomodulatory cytokines. However, their immunomodulatory features strongly depend on the molecular cross-talk between cells and the surrounding microenvironment. Hence, ...
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Mesenchymal stem/stromal cells (MSCs) as one of the most important types of adult stem cells secrete a variety of immunomodulatory cytokines. However, their immunomodulatory features strongly depend on the molecular cross-talk between cells and the surrounding microenvironment. Hence, some strategies were proposed to empower their beneficial effects during cell-therapeutic procedures to avoid confusing results. Licensing the cells with chemical compounds could be considered as one of the most applicable methods for induction of anti-inflammatory status in the cells. Human chorionic gonadotropin (hCG) is a pregnancy related hormone which has been shown to be essential for the establishment of a successful pregnancy. HCG supports the implantation of fetus in the maternal endometrium, due to its immunomodulatory effects. Moreover, the regulatory role of hCG has been previously mentioned in case of some autoimmune-based diseases. In the present study, the capacity of this hormone for induction of different immune-encountered genes expression was examined in primary cultures of human adipose tissue derived mesenchymal stem cells (Ad-MSCs). In this regard, Ad-MSCs were exposed to 10 IU of hCG for 72 hours. Molecular studies via quantitative Real-time PCR (qRT-PCR) experiments were performed to detect gene expression modifications based on the application of SYBR Green as the fluorescent dye and in comparison to the RPLP0 as the housekeeping gene. Results confirmed that hCG significantly upregulated TSG-6, TGF-β1, IL-1β and IL-6 expression levels comparing with the control group, while it downregulates COX-2 expression, and had no statistically significant effects on IL-10 andTDO2. In conclusion, priming Ad-MSCs with hCG may enhance the proliferation and immunoregulatory potential of these cells, although it needs further investigations to reveal involved molecular pathways.
Shadi Mehrzad; Sepideh sadat Hosseini; Madjid Momeni-Moghaddam; Moien Farshchian; Halimeh Hassanzadeh; Mahdi Mirahmadi; Fatemeh Sadeghifar; Hamid Reza Bidkhori
Abstract
Oxidative stress occurs as a result of breaking down the balance between oxidants (e.g., reactive oxygen species (ROS)) and antioxidants in cells. Several studies have shown that there is a close relationship between oxidative stress and inflammation at the sites of injury. Mesenchymal ...
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Oxidative stress occurs as a result of breaking down the balance between oxidants (e.g., reactive oxygen species (ROS)) and antioxidants in cells. Several studies have shown that there is a close relationship between oxidative stress and inflammation at the sites of injury. Mesenchymal stem cells (MSCs) are exposed to endogenous and exogenous oxidants generated during their ex vivo expansion or following in vivo transplantation. α-tocopherol (vitamin E) is a fat-soluble compound known for its anti-oxidant and anti-inflammatory properties. In many studies, the immunomodulatory effects of vitamin E have been observed in vivo. This study aimed to determine whether pretreatment of MSCs with antioxidants like vitamin E, will enhance the anti-inflammatory and immunomodulatory properties of these cells. For this purpose, adipose-derived MSCs (ASCs) were treated with vitamin E (600 μM) for 48 h. Quantitative PCR (qPCR) experiments were performed to evaluate the expression of genes related to inflammation (IL-1β, IL-6, IL-17, IL-10) or immunomodulation (TSG-6, COX-2, TDO2, TGF-β1). Results indicated that vitamin E significantly increased the expression of COX-2, TSG-6, and IL-1β genes at the mRNA level compared with the control group, while it significantly decreased IL-6 and TGF-β expressions. No effect was observed for IL-17, IL-10, and TDO2 genes. These results suggest that in vitro preconditioning of ASCs with vitamin E may allow the cells to improve their anti-inflammatory and immunoregulatory capacities. Vitamin E pretreatment could lead to the improvement of their therapeutic abilities in conditions that are influenced by oxidative stress.
