Publications by authors named "Reza Yarani"

21 Publications

  • Page 1 of 1

Letter to Editor in response to the article "Vitamin D insufficiency as a potential culprit in critical COVID-19 patients".

J Med Virol 2021 Mar 3. Epub 2021 Mar 3.

Medical Technology Research Center (MTRC), School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

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http://dx.doi.org/10.1002/jmv.26912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013352PMC
March 2021

Human pathways in animal models: possibilities and limitations.

Nucleic Acids Res 2021 02;49(4):1859-1871

Center for non-coding RNA in Technology and Health, University of Copenhagen, 1871 Frederiksberg, Denmark.

Animal models are crucial for advancing our knowledge about the molecular pathways involved in human diseases. However, it remains unclear to what extent tissue expression of pathways in healthy individuals is conserved between species. In addition, organism-specific information on pathways in animal models is often lacking. Within these limitations, we explore the possibilities that arise from publicly available data for the animal models mouse, rat, and pig. We approximate the animal pathways activity by integrating the human counterparts of curated pathways with tissue expression data from the models. Specifically, we compare whether the animal orthologs of the human genes are expressed in the same tissue. This is complicated by the lower coverage and worse quality of data in rat and pig as compared to mouse. Despite that, from 203 human KEGG pathways and the seven tissues with best experimental coverage, we identify 95 distinct pathways, for which the tissue expression in one animal model agrees better with human than the others. Our systematic pathway-tissue comparison between human and three animal modes points to specific similarities with human and to distinct differences among the animal models, thereby suggesting the most suitable organism for modeling a human pathway or tissue.
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http://dx.doi.org/10.1093/nar/gkab012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913694PMC
February 2021

Perfluorocarbon as an adjuvant for tumor anti-angiogenic therapy: Relevance to hypoxia and HIF-1.

Med Hypotheses 2021 Jan 10;146:110357. Epub 2020 Nov 10.

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Lack of vascularization results in increased demand for oxygen and creates a defined feature of the tumor microenvironment known as tumor hypoxia. It is well established that in response to hypoxia, hypoxia-inducible factor-1 α (HIF-1α) is induced which is an important factor in angiogenesis, invasion and metastasis. In turn, HIF-1α regulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF). Ascribed to abnormal characteristics of tumor angiogenic networks, antiangiogenic therapy approaches can even worsen the hypoxic condition and can create cancer cells with stemness features. Hence oxygen delivery via perfluorocarbon (PFC) to hypoxic sites seems to result in unstable HIF expression and consequent inactivation of angiogenesis cascade and metastasis and therefore, inhibition of cancer cells stemness.
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http://dx.doi.org/10.1016/j.mehy.2020.110357DOI Listing
January 2021

The emerging role of targeting cancer metabolism for cancer therapy.

Tumour Biol 2020 Oct;42(10):1010428320965284

Medical Biology Research Center, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Glucose, as the main consuming nutrient of the body, faces different destinies in cancer cells. Glycolysis, oxidative phosphorylation, and pentose phosphate pathways produce different glucose-derived metabolites and thus affect cells' bioenergetics differently. Tumor cells' dependency to aerobic glycolysis and other cancer-specific metabolism changes are known as the cancer hallmarks, distinct cancer cells from normal cells. Therefore, these tumor-specific characteristics receive the limelight as targets for cancer therapy. Glutamine, serine, and fatty acid oxidation together with 5-lipoxygenase are main pathways that have attracted lots of attention for cancer therapy. In this review, we not only discuss different tumor metabolism aspects but also discuss the metabolism roles in the promotion of cancer cells at different stages and their difference with normal cells. Besides, we dissect the inhibitors potential in blocking the main metabolic pathways to introduce the effective and non-effective inhibitors in the field.
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http://dx.doi.org/10.1177/1010428320965284DOI Listing
October 2020

Deciphering inhibitory activity of flavonoids against tau protein kinases: a coupled molecular docking and quantum chemical study.

J Biomol Struct Dyn 2020 Sep 8:1-14. Epub 2020 Sep 8.

Department of Chemistry, Federal University of Lavras, Lavras, Brazil.

Today, Alzheimer's disease (AD) is one of the most important neurodegenerative disorders that affected millions of people worldwide. Hundreds of academic investigations highlighted the potential roles of natural metabolites in the cornerstone of AD prevention. Nevertheless, alkaloids are only metabolites that successfully showed promising clinical therapeutic effects on the prevention of AD. In this regard, other plant metabolites such as flavonoids are also considered as promising substances in the improvement of AD complications. The lack of data on molecular mode of action of flavonoids inside brain tissues, and their potential to transport across the blood-brain barrier, a physical hindrance between bloodstream and brain tissues, limited the large-scale application of these compounds for AD therapy programs. Herein, a coupled docking and quantum study was applied to determine the binding mode of flavonoids and three protein kinases involved in the pathogenesis of AD. The results suggested that all docked metabolites showed considerable binding affinity to interact with target receptors, but some compounds possessed higher binding energy values. Because docking simulation cannot entirely reveal the potential roles of ligand substructures in the interaction with target residues, quantum chemical analyses (QCAs) were performed to cover this drawback. Accordingly, QCAs determined that distribution of molecular orbitals have a pivotal function in the determination of the type of reaction between ligands and receptors; therefore, using such quantum chemical descriptors may correct the results of virtual docking outcomes to highlight promising backbones for further developments. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1814868DOI Listing
September 2020

The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells.

Mol Cell Endocrinol 2020 12 16;518:110993. Epub 2020 Aug 16.

Translational Type 1 Diabetes Research, Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, DK-2820, Gentofte, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen N, Denmark. Electronic address:

The type 1 diabetes (T1D) risk locus on chromosome 15q25.1 harbors the candidate gene CTSH (cathepsin H). We previously demonstrated that CTSH regulates β-cell function in vitro and in vivo. CTSH overexpression protected insulin-secreting INS-1 cells against cytokine-induced apoptosis. The purpose of the present study was to identify the genes through which CTSH mediates its protective effects. Microarray analysis identified 63 annotated genes differentially expressed between CTSH-overexpressing INS-1 cells and control cells treated with interleukin-1β and interferon-γ for up to 16h. Permutation test identified 10 significant genes across all time-points: Elmod1, Fam49a, Gas7, Gna15, Msrb3, Nox1, Ptgs1, Rac2, Scn7a and Ttn. Pathway analysis identified the "Inflammation mediated by chemokine and cytokine signaling pathway" with Gna15, Ptgs1 and Rac2 as significant. Knockdown of Rac2 abolished the protective effect of CTSH overexpression on cytokine-induced apoptosis, suggesting that the small GTPase and T1D candidate gene Rac2 contributes to the anti-apoptotic effect of CTSH.
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http://dx.doi.org/10.1016/j.mce.2020.110993DOI Listing
December 2020

A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression.

BMC Complement Med Ther 2020 Jul 3;20(1):207. Epub 2020 Jul 3.

Department of Traditional Medicine, School of Medicine, Shahed University, 1471, North Kargar, Engelab Square, Tehran, Iran.

Background: Depression has rapidly progressed worldwide, and the need for an efficient treatment with low side effect has risen. Melissa officinalis L and Lavandula angustifolia Mill have been traditionally used in Asia for the treatment of depression. Many textbooks of traditional Persian medicine refer to these herbs for the treatment of depression while there are no adequate clinical trials to support this claim. The present study aimed to evaluate the efficacy of M. officinalis and L. angustifolia compared to fluoxetine for the treatment of mild to moderate depression in an 8-week randomized, double-blind clinical trial.

Methods: Forty-five adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) for major depression, were randomly assigned to 3 groups to daily receive either M. officinalis (2 g) or L. angustifolia (2 g) or fluoxetine (20 mg) and were assessed in weeks 0, 2, 4 and 8 by the Hamilton Rating Scale for Depression (HAM-D) including 17 items.

Results: Our study showed that M. officinalis and L. angustifolia effect similar to fluoxetine in mild to moderate depression. (F = 0.131, df = 2,42, p = 0.877).

Conclusion: Due to some restrictions in this study including absence of placebo group, large-scale trials are needed to investigate the anti-depressant effect of these two herbs with more details.

Trial Registration: IRCT2014061718126N1 . Registration date: 2015-06-04-"Retrospectively registered".
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http://dx.doi.org/10.1186/s12906-020-03003-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333290PMC
July 2020

Anti-diabetic potential of plant alkaloids: Revisiting current findings and future perspectives.

Pharmacol Res 2020 05 24;155:104723. Epub 2020 Feb 24.

University of Belgrade, Faculty of Agriculture, Department of Food Technology and Biochemistry, 11080 Belgrade, Serbia.

Diabetes mellitus (DM) is a chronic metabolic disease which causes millions of death all over the world each year, and its incidence is on increase. The most prevalent form, type 2 DM, is characterized by insulin resistance and β-cell dysfunction, whereas type 1 DM is due to insulin deficiency as a result of β-cell destruction. Various classes of synthetic drugs have been developed to regulate glucose homeostasis and combat the development of late-diabetic complications. However, several of these chemical agents are either sub-optimal in their effect and/or may have side effects. Biologically, alkaloids unveiled a wide range of therapeutic effects including anti-diabetic properties. The chemical backbones of these compounds have the potential to interact with a wide range of proteins involved in glucose homeostasis, and thus they have received increasing attention as reliable candidates for drug development. This review sets out to investigate the anti-diabetic potential of plant alkaloids (PAs), and therefore, scientific databases were comprehensively screened to highlight the biological activity of 78 PAs with a considerable anti-diabetic profile. There are not enough clinical data available for these phytochemicals to follow their fingerprint in human, but current studies generally recommending PAs as potent α-glucosidase inhibitors. Except for some classes of monoterpene alkaloids, other compounds showed similar features as well as the presently available anti-diabetic drugs such as amino sugars and other relevant drugs. Moreover, the evidence suggests that PAs have the potential to be used as alternative additives for the treatment of DM, however, further in vitro and in vivo studies are needed to validate these findings.
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http://dx.doi.org/10.1016/j.phrs.2020.104723DOI Listing
May 2020

Breast Milk-Derived Extracellular Vesicles Enriched in Exosomes From Mothers With Type 1 Diabetes Contain Aberrant Levels of microRNAs.

Front Immunol 2019 25;10:2543. Epub 2019 Oct 25.

Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

The breast milk plays a crucial role in shaping the initial intestinal microbiota and mucosal immunity of the infant. Interestingly, breastfeeding has proven to be protective against the early onset of immune-mediated diseases including type 1 diabetes. Studies have shown that exosomes from human breast milk are enriched in immune-modulating miRNAs suggesting that exosomal miRNAs (exomiRs) transferred to the infant could play a critical role in the development of the infant's immune system. We extracted exomiRs from breast milk of 52 lactating mothers (26 mothers with type 1 diabetes and 26 healthy mothers), to identify any differences in the exomiR content between the two groups. Small RNA-sequencing was performed to identify known and novel miRNAs in both groups. A total of 631 exomiRs were detected by small RNA sequencing including immune-related miRNAs such as hsa-let-7c, hsa-miR-21, hsa-miR-34a, hsa-miR-146b, and hsa-miR-200b. In addition, ~200 novel miRNAs were identified in both type 1 diabetes and control samples. Among the known miRNAs, nine exomiR's were found differentially expressed in mothers with type 1 diabetes compared to healthy mothers. The highly up-regulated miRNAs, hsa-miR-4497, and hsa-miR-3178, increased lipopolysaccharide-induced expression and secretion of tumor necrosis factor α (TNFα) in human monocytes. The up-regulated miRNA target genes were significantly enriched for longevity-regulating pathways and FoxO signaling. Our findings suggest a role of breast milk-derived exomiRs in modulating the infant's immune system.
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http://dx.doi.org/10.3389/fimmu.2019.02543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823203PMC
November 2020

First Report of a Disease by Rhazes 10 Centuries Ago.

Int J Prev Med 2019 15;10. Epub 2019 Jan 15.

Department of Anesthesiology and Intensive Care Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Introduction: Abu Bakr Mohammad Ibn Zakariya Al-Razi (865-925 CE), who was known as "Rhazes" in the west, was a famous scientist of medieval ages. He has more than 200 books and treatises. His masterpiece on medicine "" contains around 900 case reports. Some of the diseases which seem to be recently reported have been stated previously, but not well described. Considering symptoms of the patient described at that time, differential diagnosis will be discussed.

Case Presentation: Rhazes described a patient with bilious fever. He had developed bloody urine and stool on the fourth day and fatigue. Subsequently, the patient's urine and stool color turned into dark and black, respectively, and died the following day. According to Rhazes attitude, it was malignant measles. Meyerhof in his book has referred to post-measles acute glomerulonephritis, but more appropriate differential diagnoses are compatible with this patient.

Discussion: One of the best diagnoses for this case can be Weil's syndrome. Presence of fever, icterus, hemorrhage and renal injury, all suggest Weil's syndrome without pulmonary involvement. The other probable diagnosis is thrombotic thrombocytopenic purpura (TTP). Meningococcal sepsis is the other possible diagnosis.

Conclusion: To sum up, as three compatible diseases with the case; have been described more than a thousand years after Rhazes (Weil's syndrome 1886, TTP 1925 and meningococcemia 1805); if the case is either Weil's or TTP or meningococcal sepsis, it is the first report of the disease in the world by Rhazes.
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http://dx.doi.org/10.4103/ijpvm.IJPVM_216_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360843PMC
January 2019

The emerging role of lncRNAs in inflammatory bowel disease.

Exp Mol Med 2018 12 6;50(12):1-14. Epub 2018 Dec 6.

Type 1 Diabetes Biology, Department of Clinical Research, Steno Diabetes Center Copenhagen, Copenhagen, Denmark.

Dysregulation of long noncoding RNA (lncRNA) expression is linked to the development of various diseases. Recently, an emerging body of evidence has indicated that lncRNAs play important roles in the pathogenesis of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative Colitis (UC). In IBD, lncRNAs have been shown to be involved in diverse processes, including the regulation of intestinal epithelial cell apoptosis, association with lipid metabolism, and cell-cell interactions, thereby enhancing inflammation and the functional regulation of regulatory T cells. In this review, we aim to summarize the current knowledge regarding the role of lncRNAs in IBD and highlight potential avenues for future investigation. We also collate potentially immune-relevant, IBD-associated lncRNAs identified through a built-by association analysis with respect to their neighboring protein-coding genes within IBD-susceptible loci. We further underscore their importance by highlighting their enrichment for various aspects of immune system regulation, including antigen processing/presentation, immune cell proliferation and differentiation, and chronic inflammatory responses. Finally, we summarize the potential of lncRNAs as diagnostic biomarkers in IBD.
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http://dx.doi.org/10.1038/s12276-018-0188-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283835PMC
December 2018

L-arginine/5-fluorouracil combination treatment approaches cells selectively: Rescuing endothelial cells while killing MDA-MB-468 breast cancer cells.

Food Chem Toxicol 2019 Jan 10;123:399-411. Epub 2018 Nov 10.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Reducing the adverse effects of chemotherapy on normal cells such as endothelial cells is a determinant factor of treatment success especially in pregnant women. In this regard, modulatory effect of L-arginine on various cancers is still a controversial topic in cancer therapy. So, this study aimed to compare the effect of L-arginine treatment alone and in combination with 5-fluorouracil (5-FU) on the survival and angiogenesis of primary human umbilical vein endothelial cells (HUVECs) and the breast cancer cell line of MDA-MB-468. Combinations of L-arginine and 5-FU increased cell survival in HUVECs but induced cell death in MDA-MB-468 cells. Nitric oxide assay showed an increase of this molecule in both cell lines. Assessments of metabolic changes as well as molecular docking indicated a decrease in glycolytic activity of cancer cells but not normal cells. Angiogenesis induction in HUVECs was confirmed through VEGF and MMP-2,9 up-regulated gene expressions. However, a down-regulation of the above-mentioned genes expression was observed in MDA-MB-468. Furthermore, an in vivo increased angiogenesis and decreased embryo toxicity was observed in combination treatment. Altogether, these findings clearly suggest that L-arginine inhibits cell death induced by 5-FU in HUVECs through attenuating the adverse effects of 5-FU, while it does not do so in breast cancer cells.
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http://dx.doi.org/10.1016/j.fct.2018.11.018DOI Listing
January 2019

2-Methylpyridine-1-ium-1-sulfonate as an Inducer of Apoptosis and Cell Cycle Arrest: A comparative in vitro and Computational Study.

Nutr Cancer 2019 1;71(4):643-656. Epub 2018 Oct 1.

a Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.

"Let food be thy medicine and thy medicine be thy food" was expressed by Hippocrates and the health benefits of medicinal plants and natural products have been considered by humans since historic times. The current study aims to investigate the anti-cancer activity of 2-Methylpyridine-1-ium-1-sulfonate (MPS) isolated from bulbs of Allium hirtifolium. The MPS compound (in a dose-dependent manner) induced arrest the AGS cells in G1 and G2/M phases, and Caco-2 cells in G1 and S phases. These findings were associated with the down-regulation of cyclin D1, CDK4, and up-regulation of p21, p27 and p53. According to the morphological observations and DNA fragmentation assay, the MPS compound induced apoptosis in both cell lines, and also cause a significant increase in the expression of Bax/Bcl-2. In this context, our molecular docking results unveiled that the MPS compound has considerable affinity to interact with the minor groove of ctDNA and also with cell cycle kinases. To approve and find the accurate MPS mode of action against cancer cell lines (especially in gastrointestinal cancer) further studies is highly recommended.
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http://dx.doi.org/10.1080/01635581.2018.1506495DOI Listing
May 2020

Effective photo-enhancement of cellular activity of fluorophore-octaarginine antisense PNA conjugates correlates with singlet oxygen formation, endosomal escape and chromophore lipophilicity.

Sci Rep 2018 01 12;8(1):638. Epub 2018 Jan 12.

Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Photochemical internalization (PCI) is a cellular drug delivery method based on the generation of light-induced reactive oxygen species (ROS) causing damage to the endosomal membrane and thereby resulting in drug release to the cytoplasm. In our study a series of antisense fluorophore octaarginine peptide nucleic acid (PNA) conjugates were investigated in terms of PCI assisted cellular activity. It is found that tetramethylrhodamine and Alexa Fluor 555 conjugated octaarginine PNA upon irradiation exhibit more than ten-fold increase in antisense activity in the HeLa pLuc705 luciferase splice correction assay. An analogous fluorescein conjugate did not show any significant enhancement due to photobleaching, and neither did an Alexa Fluor 488 conjugate. Using fluorescence microscopy a correlation between endosomal escape and antisense activity was demonstrated, and in parallel a correlation to localized formation of ROS assigned primarily to singlet oxygen was also observed. The results show that tetramethylrhodamine (and to lesser extent Alexa Fluor 555) conjugated octaarginine PNAs are as effectively delivered to the cytosol compartment by PCI as by chloroquine assisted delivery and also indicate that efficient photodynamic endosomal escape is strongly dependent on the quantum yield for photochemical singlet oxygen formation, photostability as well as the lipophilicity of the chromophore.
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http://dx.doi.org/10.1038/s41598-017-18947-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766568PMC
January 2018

Multiple sclerosis influences on the augmentation of serum Klotho concentration.

J Neurol Sci 2016 Mar 6;362:69-72. Epub 2016 Jan 6.

Iranian Centre of Neurological Research, Department of Neurology Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

We have already shown that the concentration of secreted form of Klotho decreases in the cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis (RRMS). The current study aimed at assessing possible changes in the serum Klotho concentration of MS patients. Participants involved 15 new cases of RRMS patients in the relapse phase, 15 RRMS patients who had been suffering from the disease for more than three years and were under regular treatments (interferon beta-1a) and, finally, 15 non-MS patients who constituted the control group. Beside thorough neurological examinations, demographic and clinical data (e.g. gender, age, duration of disease and expanded disability status scale) were obtained. Serum Klotho concentration was measured using ELISA method. The results showed no statistically meaningful difference between new cases of RRMS (585.56pg/ml±153.99) and control group (556.81pg/ml±120.36; P=0.859). The serum Klotho level, however, was significantly higher in patients with prolonged disease duration (696.94pg/ml±170.52; P=0.037) in comparison with the subjects in the control group. In conclusion, this study showed that serum Klotho concentration tends to be higher in MS patients when compared to control group. This finding might be attributed to treatment of MS patients with immunomodulatory drugs or a compensatory response to enhance CNS regeneration and/or vitamin D biosynthesis. Further studies are required to elucidate the role of Klotho in MS pathophysiology.
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http://dx.doi.org/10.1016/j.jns.2016.01.012DOI Listing
March 2016

Differentiation of human skin-derived precursor cells into functional islet-like insulin-producing cell clusters.

In Vitro Cell Dev Biol Anim 2015 Jun 29;51(6):595-603. Epub 2015 Jan 29.

Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran.

Advances in cell-replacement strategies for diabetes have focused on renewable sources of glucose-responsive, insulin-producing cells (IPCs). One of the most proper alternatives is multipotent skin-derived precursors cells (SKPs), which can be differentiated into IPCs. In this study, we reported the isolation and expansion of human skin-derived precursors (hSKPs) followed by their differentiation into IPCs in vitro, through exposure to suitable differentiation factors. The gene expression of endocrine β cell markers was analyzed by reverse transcriptase-polymerase chain reaction. In addition, insulin production was examined immunocytochemically, and insulin and C-peptide secretion were examined using enzyme-linked immunosorbent assay. Dithizone-stained cellular clusters were observed after approximately 20 d. The clusters were found to be immunoreactive to insulin and expressed multiple genes related to pancreatic β cell development and function: insulin, Pdx-1, Islet-1, NeuroD, Glut-2, Pax-4, Ngn-3, and Nkx2.2, but not to other pancreas-specific hormones such as glucagon and somatostatin. Cellular clusters were also able to secrete detectable amounts of insulin and C-peptide in a glucose dose-dependent manner. These findings suggest that human SKPs can differentiate into functional IPCs. This may offer a safer cell source for future stem cell-based therapies.
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http://dx.doi.org/10.1007/s11626-015-9866-2DOI Listing
June 2015

In vitro inhibition of angiogenesis by heat and low pH stable hydroalcoholic extract of Peganum harmala seeds via inhibition of cell proliferation and suppression of VEGF secretion.

Pharm Biol 2015 Jun 4;53(6):855-61. Epub 2014 Dec 4.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran .

Context: Progression of cancer cells is completely dependent on its angiogenesis. Inhibition of tumor angiogenesis has shed new light on cancer treatment. As a result, anti-angiogenesis therapy represents one of the most significant advances in clinical oncology. Peganum harmala L. (Zygophyllaceae) is a native plant from the eastern Iranian region, which is used as a traditional folk medicine. Although some biological properties of this plant are determined, its effect on angiogenesis is still unclear.

Objective: We investigated the anti-angiogenic effects of heat and low pH stable hydroalcoholic extract of P. harmala seeds on endothelial cells (ECs) proliferation and VEGF secretion.

Materials And Methods: Dried Peganum seeds were purchased from Kermanshah Traditional Bazar in 2011. Hydroalcoholic extract of dried seeds (0, 10, 20, 40, 60, 80, 100, 120, and 150 μg/ml) was used for in vitro evaluation of its cytotoxicity, anti-proliferative, and anti-angiogenic effects on ECs. In vitro effect of the extract on VEGF secretion was assayed using ELISA.

Results: Treatment with hydroalcoholic extract at seven different concentrations resulted in significant decrease of ECs proliferation and angiogenesis with an ID50 of ∼ 85 μg/ml. VEGF secretion was (inhibited) decreased by the extracts at concentrations higher than 10 μg/ml.

Discussion And Conclusion: Herbal plant extracts still attract attention owing to their fewer side effects comparing to synthetic drug agents. Current study indicated that hydroalcoholic extract of P. harmala seeds contains a potent anti-angiogenic component, which exerts its inhibitory effect mainly through down-regulation of essential mediators such as VEGF.
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http://dx.doi.org/10.3109/13880209.2014.946057DOI Listing
June 2015

Proteolytic activities of kiwifruit actinidin (Actinidia deliciosa cv. Hayward) on different fibrous and globular proteins: a comparative study of actinidin with papain.

Appl Biochem Biotechnol 2014 Apr 7;172(8):4025-37. Epub 2014 Mar 7.

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Actinidin, a member of the papain-like family of cysteine proteases, is abundant in kiwifruit. To date, a few studies have been provided to investigate the proteolytic activity and substrate specificity of actinidin on native proteins. Herein, the proteolytic activity of actinidin was compared to papain on several different fibrous and globular proteins under neutral, acidic and basic conditions. The digested samples were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and densitometry to assess the proteolytic effect. Furthermore, the levels of free amino nitrogen (FAN) of the treated samples were determined using the ninhydrin colorimetric method. The findings showed that actinidin has no or limited proteolytic effect on globular proteins such as immunoglobulins including sheep IgG, rabbit IgG, chicken IgY and fish IgM, bovine serum albumin (BSA), lipid transfer protein (LTP), and whey proteins (α-lactalbumin and β-lactoglobulin) compared to papain. In contrast to globular proteins, actinidin could hydrolyze collagen and fibrinogen perfectly at neutral and mild basic pHs. Moreover, this enzyme could digest pure α-casein and major subunits of micellar casein especially in acidic pHs. Taken together, the data indicated that actinidin has narrow substrate specificity with the highest enzymatic activity for the collagen and fibrinogen substrates. The results describe the actinidin as a mild plant protease useful for many special applications such as cell isolation from different tissues and some food industries as a mixture formula with other relevant proteases.
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http://dx.doi.org/10.1007/s12010-014-0812-7DOI Listing
April 2014

New procedure for epidermal cell isolation using kiwi fruit actinidin, and improved culture of melanocytes in the presence of leukaemia inhibitory factor and forskolin.

Cell Prolif 2013 Jun 10;46(3):348-55. Epub 2013 May 10.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Objectives: Conventional isolation of epidermis from the dermis and disruption of epidermal sheets to liberate the cells, are performed using proteolytic enzymes such as thermolysin or collagenase. Selective population expansion of melanocytes is achieved by suppressing proliferation of keratinocytes and fibroblasts in epidermal cell suspensions, using phorbol esters and cholera toxin. Here, we introduce a new procedure for isolation of epidermal cells, using proteolytic activity of kiwi fruit actinidin, and also an improved growth medium for melanocytes in the presence of leukaemia inhibitory factor (LIF) and forskolin.

Materials And Methods: Dermo-epidermal separation and epidermal sheet cell dispersion were performed using actinidin compared to conventional proteases including collagenase, thermolysin or trypsin. Thereafter, melanocyte culture was performed in two common media and one modified medium to discover optimization for these cells.

Results: We found that dermo-epidermal separation and epidermal sheet cell dispersion using kiwi fruit actinidin were considerably better than previously used methods, both from the aspect of less fibroblast and keratinocyte contamination, and of more viable native cells. Also, melanocytes proliferated better in phorbol ester- and cholera toxin-free proliferation medium supplemented with LIF and forskolin.

Conclusion: Less contamination and higher numbers of viable cells were actinidin preferential for separation of epidermis and isolation of epidermal cells. Supplementation of LIF and forskolin to new medium increased proliferation potential of melanocytes in comparison to exogenous mitogens.
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http://dx.doi.org/10.1111/cpr.12028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6496922PMC
June 2013

In vitro inhibition of angiogenesis by hydroalcoholic extract of oak (Quercus infectoria) acorn shell via suppressing VEGF, MMP-2, and MMP-9 secretion.

Pharm Biol 2013 Mar 8;51(3):361-8. Epub 2012 Nov 8.

Medical Biology Research Center and Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Context: Angiogenesis is an essential factor for cancer progression. Although more attention is paid in angiogenesis on its role in cancer biology, many other non-neoplastic diseases are also angiogenic-dependent. Recently, there is motivation to control cancer via inhibition of angiogenesis.

Objective: Quercus infectoria Olivier var (Fagaceae) (oak) is a plant whose different parts, such as its fruit shell, have been used extensively as a traditional drug in the west part of Iran. Although some biological properties of oak are determined, its effects on angiogenesis are unclear. So, we investigated the antiangiogenic effects of oak acorn shell.

Materials And Methods: Fresh oak acorns were collected, and after authentication; hydroalcoholic extract of acorn shells (5, 10, 20, 30, 40, 60, 80, and 100 μg/ml) was used for evaluation of its cytotoxicity, antiproliferative, and antiangiogenic effects in vitro. Also, effects of the extract on vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and MMP-9 secretion were assayed using enzyme-linked immunosorbent assay (ELISA) and gelatin zymography.

Results: Treatment with hydroalcoholic extract in eight doses resulted in a significant decrease of endothelial cell proliferation and angiogenesis with an IC₅₀ value of ~20 μg/ml, without any toxic effect. At 40 μg/ml, the extract inhibited MMP-9 activity; however, a dose-dependent reduction (60-80 µg/ml) in MMP-2 activity was seen. VEGF secretion was decreased with increase in the concentration of the extract from 5 to 100 μg/ml.

Discussion And Conclusion: This study indicated that hydroalcoholic extract of oak acorn shell acts as a potent antiangiogenic agent which exerts its inhibitory effect mainly through downregulation of essential mediators such as VEGF and MMPs.
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http://dx.doi.org/10.3109/13880209.2012.729147DOI Listing
March 2013

Association between cholesteryl ester transfer protein TaqIB variants and risk of coronary artery disease and diabetes mellitus in the population of western Iran.

Genet Test Mol Biomarkers 2011 Nov 20;15(11):813-9. Epub 2011 Jun 20.

Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Aims: To shed light on the previously inconsistent results about the association of cholesteryl ester transfer protein TaqIB (CETP TaqIB) variants, high-density lipoprotein cholesterol (HDL-C) levels, and the risk of coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM).

Methods: To determine the frequency of CETP TaqIB variants and to examine the possible association between CETP TaqIB polymorphism with CAD and T2DM, we studied 207 unrelated patients with CAD, 101 patients with T2DM, and 92 controls. The CETP TaqIB variants were detected by polymerase chain reaction-restriction fragment length polymorphism.

Results: Logistic regression analysis indicated that the B1 allele of CETP was significantly associated with increased risk of CAD (odds ratio, OR 1.65 [95% confidence interval, CI 1.2-2.3, p=0.005]) and T2DM (OR 1.7 [95% CI 1.13-2.54, p=0.005]). Adjusted logistic regression analysis for the effects of age, sex, hypertension, diabetes, and hyperlipidemia was performed; and a significant association was found between the B1 allele and risk of CAD (OR 1.9 [95% CI 1-3.6, p=0.049]) in patients with CAD. There were no associations between the CETP alleles and the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, and HDL-C in studied groups.

Conclusions: The results of the present study revealed that the CETP B1 allele is associated with increased risk of CAD and T2DM independent of plasma HDL-C level in our population.
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http://dx.doi.org/10.1089/gtmb.2011.0037DOI Listing
November 2011