2024-03-29T14:13:09Z
https://ijbms.mums.ac.ir/?_action=export&rf=summon&issue=2104
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
The effect of Elettaria cardamomum (cardamom) on the metabolic syndrome: Narrative review
Roghayeh
Yahyazadeh
Mahboobeh
Ghasemzadeh Rahbardar
Bibi Marjan
Razavi
Gholamreza
Karimi
Hossein
Hosseinzadeh
Metabolic syndrome (MetS), as a health-threatening factor, consists of various symptoms including insulin resistance, high blood sugar, hypertension, dyslipidemia, inflammation, and abdominal obesity that raise the risk of diabetes mellitus and cardiovascular disease. Cardiovascular diseases are important causes of mortality among the world population. Recently, there has been a growing interest in using phytomedicine and natural compounds in the prevention and treatment of various diseases. The data was gathered by searching various standard electronic databases (Google Scholar, Scopus, Web of Science, and PubMed) for English articles with no time limitations. All in vivo, in vitro, and clinical studies were included. Elettaria cardamomum (cardamom) is a rich source of phenolic compounds, volatile oils, and fixed oils. Cardamom and its pharmacologically effective substances have shown broad-spectrum activities including antihypertensive, anti-oxidant, lipid-modifying, anti-inflammatory, anti-atherosclerotic, anti-thrombotic, hepatoprotective, hypocholesterolemic, anti-obesity, and antidiabetic effects. This review aims to highlight the therapeutic effects of cardamom on MetS and its components including diabetes, hyperlipidemia, obesity, and high blood pressure as well as the underlying mechanisms in the management of MetS. Finally, it can be stated that cardamom has beneficial effects on the treatment of MetS and its complications.
Anti-inflammatory agents
Anti-Oxidants
Elettaria cardamomum
Hypoglycemic agents
Hypolipidemic agents
metabolic syndrome
2021
11
01
1462
1469
https://ijbms.mums.ac.ir/article_18871_604104730dfdddf6a2c617be448567b2.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Comprehensive bioinformatic analysis reveals oncogenic role of H2A.Z isoforms in cervical cancer progression
Eric
Salmerón-Bárcenas
Ana
Zacapala-Gómez
Daniela
Lozano-Amado
Leonardo
Castro-Muñoz
Marco
Leyva-Vázquez
Joaquín
Manzo-Merino
Pedro
Ávila-López
Objective(s): Cervical cancer ranks as the fourth most common neoplasia in women worldwide in which epigenetic alterations play an important role. Several studies have reported pro-oncogenic role of the histone variant H2A.Z in different types of cancer; however, the role of H2A.Z in cervical cancer remains poorly studied. This study aimed to determine the potential role of H2A.Z in cervical cancer through a bioinformatic approach.Materials and Methods: H2A.Z expression was analyzed in The Human Protein Atlas, The Cancer Genome Atlas, and Gene Expression Omnibus datasets. The promoter regions of H2AZ1 and H2AZ2 genes were downloaded from Expasy, and the prediction of transcription factor binding motifs was performed using CONSITE, Alibaba, and ALGGEN. ChIP-seq and RNA-seq data from HeLa-S3 cells were downloaded from ENCODE. The discovery motif was investigated using MEME-ChIP. The functional annotation was examined in Enrich.Results: The expression of H2A.Z is elevated in cervical cancer. Interestingly, DNA methylation, copy number, and transcription factors AP2α and ELK1 are involved in H2A.Z overexpression. Additionally, H2A.Z is enriched on promoter and enhancer regions of genes involved in pathways associated with cancer development. In these regions, H2A.Z enables the recruitment of transcription factors such as NRF1, NFYA, and RNA Pol II. Finally, H2A.Z allows the expression of genes associated with proliferation in patients with cervical cancer.Conclusion: Our findings suggest that H2A.Z overexpression and its presence in promoters and enhancers could be regulating the transcription of genes involved in cervical carcinogenesis.
Cervical Cancer
Enhancers
H2A.Z
H2A.Z isoforms
Promoters
Proliferation
2021
11
01
1470
1481
https://ijbms.mums.ac.ir/article_18961_cbd0dbf8cb2db0066117a9ee5983128c.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Changes in the expression of the B subunit of vacuolar H+-ATPase, in the hippocampus, following transient forebrain ischemia in gerbils
Hyo Young
Jung
Woosuk
Kim
Kyu Ri
Hahn
Min Soo
Kang
Hyun Jung
Kwon
Jung Hoon
Choi
Yeo Sung
Yoon
Dae Won
Kim
Dae Young
Yoo
Moo-Ho
Won
In Koo
Hwang
Objective(s): Vacuolar H+-ATPase is a highly conserved enzyme that plays an important role in maintaining an acidic environment for lysosomal function and accumulating neurotransmitters in synaptic vesicles. In the present study, we investigated the time-dependent changes in the expression of vacuolar H+-ATPase V1B2 (ATP6V1B2), a major neuronal subtype of vacuolar H+-ATPase located in the hippocampus, after 5 min of transient forebrain ischemia in gerbils. We also examined the pH and lactate levels in the hippocampus after ischemia to elucidate the correlation between ATP6V1B2 expression and acidosis.Materials and Methods: Transient forebrain ischemia was induced by occlusion of both common carotid arteries for 5 min and animals were sacrificed at various time points after ischemia for immunohistochemical staining of ATP6V1B2 and measurements of pH and lactate levels in the hippocampus.Results: ATP6V1B2 immunoreactivity was found to be transiently increased in the hippocampal CA1 region and dentate gyrus 12–24 hr after ischemia when the pH and lactate levels were decreased. In addition, ATP6V1B2 immunoreactivity significantly increased in the hippocampal CA3 and dentate gyrus, regions relatively resistant to ischemic damage, 4 days after ischemia, when the NeuN-positive, mature neuron numbers were significantly decreased in the hippocampal CA1 region. Conclusion: These results suggest that ATP6V1B2 expression is transiently increased in the hippocampus following ischemia, which may be intended to compensate for ischemia-related dysfunction of ATP6V1B2 in the hippocampus.
Acidosis
Cell death
Gerbils
Hippocampus
Ischemia
2021
11
01
1482
1487
https://ijbms.mums.ac.ir/article_18962_dcb67f13df7ab70b24d736823fbcef12.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Synthesis and evaluation of 99mTc-DOTA-ARA-290 as potential SPECT tracer for targeting cardiac ischemic region
Naser
Mohtavinejad
Maliheh
Hajiramezanali
Mehdi
Mehdi Akhlaghi
Ahmad
Bitarafan-Rajabi
Nazila
Gholipour
Objective(s): Myocardial infarction caused by ischemia of heart tissue is the main reason for death worldwide; therefore, early detection can reduce mortality and treatment costs. Erythropoietin (EPO) has protection effects on ischemic tissue due to nonhematopoietic peptide (pHBSP; ARA-290) which is derived from the B-subunit of EPO. Materials and Methods: We designed and synthesized a modified DOTA-(Lys-Dabcyl6, Phe7)-ARA-290 using Fmoc solid-phase peptide synthesis strategies. To improve serum stability, Fmoc-Lys-(Dabcyl)-OH as lipophilic amino acid was synthesized along with Fmoc-Phe-OH which then were substituted with Arg6 and Ala7, respectively; they were then investigated for the ability to detect ischemic cardiac imaging. DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 was labeled with technetium 99m, and its radiochemical purity (RCP), stability in the presence of human serum and, specific bind to hypoxic H9c2 cells were evaluated. In vivo studies for biodistribution and SPECT scintigraphy were checked in a normal and cardiac ischemia rat model. Results: Radiolabeling purity was obtained more than 96% by ITLC, and in vitro stability of the radiopeptide up to 6 hr was 85%. The binding of 99mTc-ARA-290 to hypoxic cells was remarkably higher than normoxic cells (3 times higher than normoxic cells at 1 hr). Biodistribution and SPECT imaging on the cardiac ischemic model showed that radiopeptide considerably accumulated in the ischemic region (cardiac ischemic-to-lung rate = 3.65 ID/g % at 0.5 hr).Conclusion: The results of studies, in vitro and in vivo, indicated that 99mTc-DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 could be an appropriate candidate for early diagnosis of cardiac ischemia.
ARA-290
Erythropoietin (EPO)
Ischemia
Molecular imaging
Technetium-99m
2021
11
01
1488
1499
https://ijbms.mums.ac.ir/article_18917_55bf9ea2244bb749c0c73bf58f8c3b61.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Effects of integrin-linked kinase on protein kinase b, glycogen synthase kinase-3β, and β-catenin molecules in ovarian cancer cells
Seda
SARI KILICASLAN
Zerrin
Seller
Objective(s): This study examines the impact of integrin-linked kinase (ILK), protein kinase B (AKT), glycogen synthase kinase-3β (GSK-3β), and β-catenin signal molecules in SKOV-3 ovarian cancer cells adhered to fibronectin. Materials and Methods: Expression levels of α4, αv, β1, and β6 integrin subunits known as the fibronectin ligand were investigated with the flow cytometry technique. The effects of ILK, AKT, GSK-3β, and β-catenin on the binding of SKOV-3 cells to fibronectin were examined by using the Real-Time Cellular Analysis (RTCA) method. Additionally, the interaction of these proteins was investigated by using Western blot analysis. Results: The results show that the expression levels of integrin subunits were ranked as αv (67.8%), followed by α4 (48.55%), β6 (32.05%), and β1 (31%) on SKOV-3 cells. RTCA results showed that ILK (10 µM Cpd22), GSK-3β (50 μM GSK-3β inhibitor-XI), AKT (35 µM FPA 124), and β-catenin (50 μM cardamonin) inhibitors decreased significantly (P<0.01) binding to fibronectin at 24 hr. Western studies in SKOV-3 cells adhered to fibronectin have shown that in inhibition of ILK, AKT expression was strongly inhibited, whereas, in the inhibition of AKT, ILK expression was strongly inhibited. Furthermore, the expression of β-catenin is partially reduced in inhibition of these two molecules. In β-catenin inhibition, AKT and ILK expressions are also strongly inhibited.Conclusion: ILK, AKT, GSK-3β, and β-catenin were found to be fundamental molecules in binding of SKOV-3 cells to fibronectin. ILK and AKT affect strongly the level of expression of each other, and both also affect the signal path of β-catenin.
Beta-catenin
Epithelial ovarian cancer
Fibronectin
GSK-3beta
Integrin
2021
11
01
1500
1508
https://ijbms.mums.ac.ir/article_18948_6837ff8e1194ea72bfb95412e3a61a98.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Inhibitory effects of tolerogenic probiotics on migratory potential of lupus patient-derived DCs
Seyed-Alireza
Esmaeili
Ramezan Ali
Taheri
Mahmoud
Mahmoudi
Amir Abbas
Momtazi-Borojeni
Mehdi
Morshedi
Ali
Bahramifar
Mahdi
Fasihi-Ramandi
Objective(s): The present in vitro study aimed to evaluate whether Lactobacillus delbrueckii and Lactobacillus rhamnosus treatments can induce regulatory phenotype, together with modulating the expression of chemokine receptors (CRs) in dendritic cells (DCs). The CRs of DCs have been found to be involved in the pathogenesis of Systemic lupus erythematosus (SLE) through directing recruitment and migration of immune cells.Materials and Methods: In brief, monocytes of patients with SLE and healthy donors were isolated and differentiated to regulatory or inflammatory mature DCs through treatment with L. delbrueckii, L. rhamnosus, mixed probiotics, and LPS. Results: FACScan analysis showed that the expression of CRs including CXCR3, CCR5, CCR4, and CCR3, was significantly reduced in all probiotic-treated groups of SLE and healthy (control) donors when compared with the LPS treated group. Conclusion: The results demonstrated that tolerogenic probiotics could prevent or decrease the expression of inflammatory CRs on the surface of tolerogenic DCs during the maturation process.
Chemokine receptor
Lactobacillus Delbrueckii
Lactobacillus Rhamnosus
systemic lupus erythematosus
Tolerogenic dendritic cell
2021
11
01
1509
1514
https://ijbms.mums.ac.ir/article_18916_77bfc4f10e7ea31f1b675c1a3777b295.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
In vitro anti-proliferative effect of capecitabine (Xeloda) combined with mocetinostat (MGCD0103) in 4T1 breast cancer cell line by immunoblotting
Hacer
Kaya Cakır
Onur
Eroglu
Objective(s): Mouse breast cancer cell line 4T1 can accurately mimic the response to immune receptors and targeting therapeutic agents. Combined therapy has emerged as an important strategy with reduced side effects and maximum therapeutic effect. Mocetinostat (MGCD0103) is one of the members of Class I Histone Deacetylase Inhibitors (HDACi) and its mechanism of action has not been defined, yet. Capecitabine (Xeloda) is an antimetabolite and currently is widely utilized to treat a wide range of solid tumors. The aim of this study was to investigate the effects of the capecitabine, mocetinostat and their combined application on the 4T1 cell line. Materials and Methods: The effects of combined administration of mocetinostat and capecitabine on 4T1 cells were investigated by cell viability and migration assays, apoptosis analysis, and Western blotting technique.Results: The concentrations of drugs that give a half-maximal response (IC50) were detected for capecitabine (1700 µM), mocetinostat (3,125 µM), and 50 µM Capecitabine+1,5 µM Mocetinostat for 48 hr. In capecitabine+mocetinostat combine group, we observed that cell migration decreased, DNA fragmentation increased compared to the control group. capecitabine + mocetinostat group induced apoptosis by decreasing Bcl-2, PI3K, Akt, c-myc protein levels, while increasing Bax, Caspase-3, PTEN, cleaved-PARP, Caspase-7, Caspase-9, p53, cleaved-Cas-9 protein levels in 4T1 cells. Conclusion: Capecitabine and mocetinostat played a toxic role through inducing apoptosis on 4T1 cancer cells in a time- and concentration-dependent manner. These results showed that combined therapy with low concentrations were detected to be more effective than that with high-concentration alone drug treatment.
Apoptosis
Breast neoplasms
Drug synergism
Capecitabine
Histone deacetylase inhibitors
2021
11
01
1515
1522
https://ijbms.mums.ac.ir/article_18942_3a210512b2bdfdd500f264801c1231c0.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Formation of organoid-like structures in the decellularized rat testis
Mehrafarin
Kiani
Mansoureh
Movahedin
Iman
Halvaei
Masoud
Soleimani
Objective(s): In testis, the extracellular matrix (ECM) in addition to the supportive role for cells in the seminiferous epithelium, is also essential for the accurate functioning of these cells. Thus, using a decellularized testicular ECM (DTECM), as a scaffold for three-dimensional (3D) culture of testicular cells can mimic native ECM for studying in vitro spermatogenesis. Materials and Methods: The rat testis was decellularized via perfusion of 0.5% sodium dodecyl sulfate (SDS) for 48 hr, followed by 1% Triton X-100 for 6 hr, and then 1% DNase I for 1 hr. The efficiency of decellularization was evaluated by histology, immunohistochemistry (IHC), scanning electron microscopy (SEM), and MTT test. The prepared scaffolds were recellularized with testicular cells and cultured and assessed with hematoxylin-eosin (H&E) staining after two weeks. Results: Based on the H&E image, no trace of cell components could be observed in DTECM. IHC images demonstrated collagen types I and IV, laminin, and fibronectin were preserved. Masson’s trichrome and alcian blue staining revealed that collagen and glycosaminoglycans (GAGs) were retained, and the SEM image indicated that 3D testicular architecture remained after the decellularization process. Based on the results of the MTT test, DTECM was cytocompatible, and H&E images represented that DTECM supports testicular cell arrangements in seminiferous tubule-like structures (STLSs) and organoid-like structures (OLSs). Conclusion: The results showed that the applied protocol successfully decellularized the testis tissue of the rat. Therefore, these scaffolds may provide an appropriate vehicle for in vitro reconstruction of the seminiferous tubule.
Decellularization
Extracellular matrix
Organoid
Seminiferous tubule
Testis
2021
11
01
1523
1528
https://ijbms.mums.ac.ir/article_18997_54dcf0be03c288fed5b78481ec3e90c2.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Metformin synergistically increases the anticancer effects of lapatinib through induction of apoptosis and modulation of Akt/AMPK pathway in SK-BR3 breast cancer cell line
Davood
Neamati
Azam
Khedri
Mohammad
Aberomand
Ali-Asghar
Hemati
Maryam
Mohammadzadeh
Kourosh
Akbari Baghbani
Ghorban
Mohammadzadeh
Objective(s): Combination chemotherapy is a beneficial intervention for breast cancer, versus single therapy. We investigated the effect of Metformin (Met) on Lapatinib (Lap)-induced apoptosis in SK-BR3 cells. Materials and Methods: Toxic effect of Met and Lap on SK-BR3 cells was measured using MTT assay. Flow cytometry was used to measure the co-treatment effect of Met on lapatinib-induced apoptosis. The relative expression of Bax, Bcl2, and P21 was measured using a real-time PCR. The activity of caspase 3 and 9 was measured using an ELISA kit. The protein level of AMPK and Akt was determined using Western blot analysis.Results: Metformin and lapatinib alone and combined form showed significant time- and dose-dependent toxic effects on SK-BR3 cell viability. The greatest synergistic inhibitory effect on the cell viability [combination index (CI) = 0.51] was remarkable at Met 100 mM combined with Lap 100 nM. The combination has a stronger apoptotic death (46%) versus lapatinib alone. The combination considerably increased the mRNA expression of Bax and P21, and caspase 3 and 9 activity, while, decreasing the mRNA expression of Bcl2. Additionally, the combination significantly up-regulated and down-regulated the protein levels of AMPK and Akt, respectively.Conclusion: The metformin-lapatinib combination can induce more potent apoptotic death versus each compound individually. The combination may be suggested as a valuable therapeutic intervention in patients with breast cancer. However, additional in vivo studies are necessary to evaluate the clinical use of the combination for induction of apoptosis and its antitumor effects.
Akt
AMPK
Apoptosis
Drug synergism
Lapatinib
Metformin
2021
11
01
1529
1537
https://ijbms.mums.ac.ir/article_19001_5e83a10977c7dcaab6f4c7aa0cbdb8bf.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Zerumbone mediates apoptosis and induces secretion of proinflammatory cytokines in breast carcinoma cell culture
Barathan
Muttiah
Kumutha Malar
Vellasamy
Zaridatul
Ibrahim
Vanitha
Mariappan
See
Hoong
Jamuna
Vadievlu
Objective(s): To investigate the potential anti-breast cancer activity of zerumbone in regulating apoptotic mediators and cytokines in comparison with paclitaxel (positive control). Materials and Methods: In this study, assays such as viability, apoptosis, reactive oxygen species, cell cycle, DNA fragmentation, and cytokines were carried out on MCF-7 cells after treatment with zerumbone and paclitaxel.Results: The results showed that zerumbone demonstrated a higher (18-fold) IC50 value (126.7 µg/ml) than paclitaxel (7.29 µg/ml) in order to suppress proliferation and induce cell death of MCF-7. The cell cycle arrest at the G0/G1 phase and excessive intracellular ROS production during the in vitro zerumbone treatment indicated occurrence of apoptotic cell death although nuclear DNA fragmentation was not observed. The flow cytometer analysis of treated cells revealed secretion of proinflammatory cytokines suggesting the potential immunomodulatory activity of zerumbone. Conclusion: Although, zerumbone exhibited a higher IC50 value compared with paclitaxel yet its anticancer activity against MCF-7 cells is still parallel to paclitaxel hence zerumbone has the potential to be an antineoplastic agent in the treatment of breast cancer especially the luminal type A.
Apoptosis
Breast
Cytokine
Natural
Zerumbone
2021
11
01
1538
1545
https://ijbms.mums.ac.ir/article_18941_93c6b8eefc3fb7c533479d6998c79869.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Recombinant hemagglutinin of swine H1N1 influenza virus expression in the insect cells: Formulation in Montanide ISA71 adjuvant and the potency studies
Sara
Zahmati
Morteza
Taghizadeh
Setareh
Haghighat
Reza
Jalali Rad
Mehdi
Mahdavi
Objective(s): Influenza is a highly contagious disease, which affects the respiratory system and seasonal influenza is common throughout the world. Influenza vaccination is an effective way to reduce the risk of death and hospitalization. This study aims at the expression of swine recombinant hemagglutinin protein in the baculovirus expression system and it offers a comparison of the immunologic parameters with the commercial vaccine. Materials and Methods: The HA gene from the swine H1N1 strain of the Influenza virus was cloned into the Bac-To-Bac expression system in pFastBAC HTA vector and was transformed into Escherichia coli TOP10 strain. After the confirmation, the vector was transfected into the SF9 insect cell line. The recombinant HA was evaluated by SDS-PAGE and western blot. After formulation in Montanide ISA71 adjuvant, the immunization test was performed comparatively with Alum adjuvant, commercial vaccine in four groups of BALB/c mice, of which one group was control without any vaccination. Two weeks after the last immunization, the antibody response was assessed with HI assay, and experimental mice were challenged with mouse-adapted Influenza A/PR8/34 (H1N1) virus through nasal inhalation. Results: The immunoassay results revealed that the candidate vaccine induced the antibody response as the commercial one did but it did not significantly reduce the mortality rate, body loss, and severe fever. Conclusion: To summarize, the results showed that the recombinant protein with the MontanideTM ISA- 71 adjuvant developed a more appropriate level of immunity than Alum adjuvant, so it might be used as a safe and reliable vaccine against H1N1 virus for further research.
Adjuvant
H1N1 subtype
Hemagglutinin
Influenza
Recombinant vaccine
2021
11
01
1546
1553
https://ijbms.mums.ac.ir/article_19047_a0f0e9b6eed05c7bad09485e609848ef.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Sperm and testicular dysfunction during cecal ligation and puncture-induced sepsis in male rats and effects of tannic acid through reducing testicular oxidative stress and inflammation
Fatemeh
Pourmirzaei
Mina
Ranjbaran
Mehri
Kadkhodaee
Farzaneh
Kianian
Keivan
Lorian
Arash
Abdi
Mahdi
Hajiaqaei
Behjat
Seifi
Objective(s): One of the problems caused by infectious diseases is the decrease in sperm count and motility. Tannic acid is known as an anti-oxidant and anti-inflammatory agent. In this study, Cecal Ligation and Puncture (CLP) sepsis model was induced to investigate the effect of tannic acid on oxidative stress and inflammation in testicular and sperm structure and function.Materials and Methods: Twenty-four male Wistar rats (250–300 g) were randomly divided into 3 groups of 8: 1) sham, 2) sepsis, and 3) sepsis + tannic acid (20 mg/kg at 6, 12, and 24 hr after sepsis induction). Thirty hours after induction of sepsis, testicular samples were collected to measure SOD activity and MDA, IL-6, and TNF-α levels. Another part of the testis was fixed in 10% formalin for histological examinations. Results: In the sepsis group, testicular MDA, TNF-α, and IL-6 levels increased and SOD activity decreased compared with the sham group. In addition, the percentage of motile sperm and the survival rate of sperm decreased significantly in the sepsis group. Administration of tannic acid significantly decreased inflammatory markers (TNF-α and IL-6) and MDA levels and increased SOD activity. Furthermore tannic acid significantly improved sperm parameters and increased sperm and animal survival rates.Conclusion: The results of this study showed that the reproductive system may be strongly affected by the conditions created during sepsis. Tannic acid improved reproductive dysfunction in sepsis by reducing oxidative stress and inflammation.
Inflammation
Oxidative stress
Sepsis
Sperm
tannic acid
Testicular dysfunction
2021
11
01
1554
1560
https://ijbms.mums.ac.ir/article_19028_68a8a2684ef0d0eec683b57dff857128.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Prognostic significance of HOXD4 protein expression in human ovarian cancers
Bo
Yu
Xiaoqing
Guo
Objective(s): Ovarian cancer is the most common gynecological malignancy, ranking as the fifth leading cause of cancer-related deaths among females in the United States. Homeobox D4 (HOXD4) is a transcription factor belonging to the homeobox protein family, which plays a critical role in morphogenesis during embryo development. Here we aimed to study the HOXD4 expression in ovarian serous carcinoma (OSC) and determine its clinical significance. Materials and Methods: Real-time quantitative PCR and immunohistochemistry targeting human OSC tissues and adjacent ovarian tissues were performed to correlate the patterns of HOXD4 expression with clinical characteristics and survival outcomes. Cell lines and nude mice were used for verifying the role of HOXD4 in OSC.Results: HOXD4 protein was predominantly expressed in OSC tissues compared with nontumorous tissues. The correlation test demonstrated a significant correlation between HOXD4 with tumor FIGO stage. Univariate and multivariate analyses found that HOXD4 expression was associated with poorer overall survival. Furthermore, high expression of HOXD4 protein was observed in OSC cell lines in vitro. Finally, the oncogenic effect of HOXD4 was confirmed by cellular and xenograft experiments.Conclusion: HOXD4 protein expression may be associated with a poorer prognosis in OSC. The unfavorable prognostic value of HOXD4 in malignancies and its underlying mechanism are worthy of further investigation.
Biomarker
Homeobox D4
Ovarian Neoplasms
Prognosis
Proliferation
2021
11
01
1561
1567
https://ijbms.mums.ac.ir/article_18879_ad048f085f5ebd3a2b116872a69e791a.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Impact of linker histone in the formation of ambochlorin-calf thymus DNA complex: Multi-spectroscopic, stopped-flow, and molecular modeling approaches
Azam
Askari
Parisa
Mokaberi
Maryam
Dareini
Morvarid
Medalian
Mahtab
Pejhan
Maryam
Erfani
Maryam
Asadzadeh-Lotfabad
Mohammad-Reza
Saberi
Jamshidkhan
Chamani
Objective(s): This study aimed to evaluate the role of the linker histone (H1) in the binding interaction between ambochlorin (Amb), and calf thymus DNA (ctDNA) as binary and ternary systems. Materials and Methods: The project was accomplished through the means of absorbance, fluorescence, stopped-flow circular dichroism spectroscopy, viscosity, thermal melting, and molecular modeling techniques.Results: Spectroscopic analysis revealed that although Amb was strongly bound to both ctDNA and ctDNA-H1, it showed a greater tendency to ctDNA in the presence of the linker histone. The obtained thermodynamic parameters revealed that both Amb-ctDNA and Amb-ctDNA-H1 interactions were spontaneous, endothermic, and entropy-favored, and hydrophobic interactions played the main role in the formation and stabilization of complexes. Analysis of the stopped-flow circular dichroism results revealed that the binding process of Amb-ctDNA and Amb-ctDNA-H1 required a time of more than 150 milliseconds to complete. Moreover, Amb-ctDNA complex formation was marginally decelerated in the presence of the linker histone. The docking results suggested that the presence of the linker histone may alter the binding sites of Amb from ctDNA minor grooves to major grooves. Conclusion: All quenching processes were governed by a dynamic mechanism. Additionally, Amb did not stabilize or induce considerable conformational changes in ctDNA and ctDNA-H1 complex upon binding. In silico molecular docking results confirmed that Amb was bound to the double-helical ctDNA and ctDNA-H1 via ctDNA grooves. In summary, some binding properties of the interactions between Amb and ctDNA change in the presence of the linker histone.
Calf thymus DNA
Linker histone
Molecular modeling
Spectroscopy
Circular dichroism
2021
11
01
1568
1582
https://ijbms.mums.ac.ir/article_19029_dbbb0142a27d256fe54defe15832d07b.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
Mesenchymal stem cells promote caspase-3 expression of SH-SY5Y neuroblastoma cells via reducing telomerase activity and telomere length
Ezzatollah
Fathi
Somayeh
Vandghanooni
Soheila
Montazersaheb
Raheleh
Farahzadi
Objective(s): The use of mesenchymal stem cells in malignancies has attracted much attention due to their ability to deliver anticancer agents to tumors, including cytokines, chemokines, etc. This study aimed to investigate the effect of MSCs on the neuroblastoma SH-SY5Y cells through proliferation/apoptosis, senescence assessment, telomere length, and telomerase activity in vitro. BAX and BCL2 were also examined as potential signaling pathways in this process.Materials and Methods: For this reason, two cell populations (MSCs and SH-SY5Y cells) were co-cultured on trans-well plates for 7 days. In a subsequent step, SH-SY5Y cells were harvested from both control and experimental groups and subjected to flow cytometry, ELISA, real-time PCR, PCR-ELISA TRAP assay, and Western blotting assay for Ki67/Caspase3 investigation, β-Galactosidase assessment, telomere length, and telomerase activity assay. Also, expression of genes and proteins through real-time PCR and Western blotting demonstrated the involvement of the aforementioned signaling pathways in this process.Results: It was found that MSCs contributed significantly to decrease and increase of Ki-67 and Caspase-3, respectively. Also, MSCs dramatically reduced the length of telomere and telomerase activity and increased the β-Galactosidase activity in a significant manner. In addition, significant increase and decrease were also seen in BAX and BCL2 gene and protein expressions, respectively. Conclusion: These findings revealed that close interaction between MSCs and neuroblastoma cells causes inhibition of the SH-SY5Y cell proliferation and promotes cell senescence via BAX and caspase-3 cascade pathways.
Caspase3
Mesenchymal stem cells
Neuroblastoma
Signaling pathways
Telomerase
Telomere
2021
11
01
1583
1589
https://ijbms.mums.ac.ir/article_19048_09bb8eefc7f48218f4c40a5ba25c1430.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
4-Hydroxy-3,5-di-tret-butyl cinnamic acid restores the activity of the hippocampal mitochondria in rats under permanent focal cerebral ischemia
Dmitry
Pozdnyakov
Objective(s): Ischemic stroke is a disease with complex pathogenesis that requires timely and rational pharmacological intervention. One possible treatment for this condition may be to improve mitochondrial function as part of neuroprotective therapy.Materials and Methods: Cerebral ischemic damage was reproduced by middle cerebral artery permanent occlusion in Wistar male rats. 4-hydroxy-3,5-di-tretbutyl cinnamic acid was injected intraperitoneally in dose range of 25 mg/kg, 50 mg/kg, and 100 mg/kg. The time of administration was 3 days from the ischemia modeling. Further, changes in the rats’ cognitive functions in the Morris water maze test were evaluated, and the state of mitochondrial function in the hippocampal tissue was studied.Results: The study showed that the use of the studied compound dose-dependently improved mitochondrial function in the rat hippocampus. At doses of 20 mg/kg and 50 mg/kg, administration of the test substance increased citrate synthase activity by 55.1% (P<0.05) and 43.4% (P<0.05), respectively and ATP content by 25.7% (P<0.05) and 23.9% (P<0.05). Also, the intensity of oxidative stress (activity of antioxidant enzymes increase whereas the concentration of TBARS reduces) and apoptosis (calcium content, concentration of apoptosis-inducing factor, and caspase-3 activity decrease; latent time of mitochondrial transition permeability pore opening increase) decreased against the background of administration of the test compound. At a dose of 100 mg/kg, the studied compound showed less effectiveness.Conclusion: Administration of 25 mg/kg and 50 mg/kg 4-hydroxy-3,5-di-tretbutyl cinnamic acid demonstrated neuroprotection action on hippocampal cells under the conditions of irreversible brain ischemia.
Apoptosis
Cerebral ischemia
Cinnamic acid derivatives
Mitochondrial dysfunction
Neuroprotection
Oxidative stress
2021
11
01
1590
1601
https://ijbms.mums.ac.ir/article_18933_43c7de9dc335690fed64b22ed81e1f0b.pdf
Iranian Journal of Basic Medical Sciences
2008-3866
2008-3866
2021
24
11
M2c Macrophages enhance phalange regeneration of amputated mice digits in an organ co-culture system
Fatemeh
Bijarchian
Leila
Taghiyar
Zahra
Azhradi
Mohamadreza
Baghaban Eslaminejad
Objective(s): Delayed anti-inflammatory responses and scar-formation are the main causes for inability of injured body parts such as phalanges to regrow in mammals. Salamanders can regenerate fully scar-free body structures, followed by the appearance of anti-inflammatory responses at the injured site immediately after amputation. This study aimed to evaluate the local regenerative effects of direct amplified anti-inflammatory signals on regeneration of amputated mice digit tips using M2c-macrophages in a co-cultured organ system for the first time. Materials and Methods: We used the amputated digits from the paws of 18.5E day old C57BL/6J mice. Monocytes were obtained from peripheral blood and co-cultured with amputated digits, which subsequently enhanced the M2c macrophage phenotype induced by IL-10. We also examined the regenerative effects of IL-10 and transcription growth factor-beta 1 (TGF-β1). Results: The regrowth of new tissue occurred 10 days post-amputation in all groups. This regrowth was related to enhanced Msh homeobox-1 (Msx1), Msh homeobox-2 (Msx2), and bone morphogenic protein-4 (Bmp4) genes. Increased expression of fibroblast growth factor-8 (Fgf-8) also increased the proliferation rate. Histological analyses indicated that epidermal-closure occurred at 3-dpa in all groups. We observed full digit tip regeneration in the co-cultured group. Particularly, there was new tissue regrowth observed with 40 µg/ml of IL-10 and 120 µg/ml of TGF-β. In contrast, the control group had no remarkable digit elongation.Conclusion: We propose that a direct amplified anti-inflammatory response at the digit injury site can regenerate epithelial and mesenchymal tissues, and might be useful for limb regeneration without scar formation in adult mammals.
Anti-inflammatory - responses
IL-10
M2c macrophage
Organ-culture
Paw regeneration
TGF-β
2021
11
01
1602
1612
https://ijbms.mums.ac.ir/article_19049_2c1973e6d511329efab835b74df34cc2.pdf