Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101The genus Cuscuta (Convolvolaceac): An updated review on indigenous uses, phytochemistry, and pharmacology122512521396410.22038/ijbms.2019.35296.8407ENShazia NoureenDepartment of Chemistry, University of Sargodha, Sargodha-40100, Pakistan0000-0002-9398-4269Sobia NoreenDepartment of Chemistry, University of Sargodha, Sargodha-40100, Pakistan0000-0002-0815-2223Shazia Akram GhummanCollege of Pharmacy, University of Sargodha, Sargodha-40100, PakistanFozia BatoolDepartment of Chemistry, University of Sargodha, Sargodha-40100, PakistanSyed Nasir Abbas BukhariDepartment of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf, Sakaka2014, Saudi Arabia0000-0001-8125-7972Journal Article20181023Cuscuta, commonly known as dodder, is a genus of family convolvolaceace. Approximately 170 species of Cuscuta are extensively distributed in temperate and subtropical areas of the world. Species of this genus are widely used as essential constituents in functional foods and traditional medicinal systems. Various parts of many members of Cuscuta have been found efficacious against a variety of diseases. Phytochemical investigations have confirmed presence of biologically active moieties such as flavonoids, alkaloids, lignans, saponines, phenolics, tannins, and fatty acids. Pharmacological studies and traditional uses of these plants have proved that they are effective antibacterial, antioxidant, antiostioporotic, hepatoprotective, anti-inflammatory, antitumor, antipyretic, antihypertensive, analgesic, anti hair fall, and antisteriogenic agents.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Conditioned medium obtained from human amniotic membrane-derived mesenchymal stem cell attenuates heart failure injury in rats125312581372310.22038/ijbms.2019.36617.8722ENSolmaz Nasseri MalekiPhysiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0003-3290-4074Nahid AboutalebPhysiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0002-7514-5939Donya NazariniaDepartment of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, IranSara Allahverdi BeikPhysiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, IranAsadollah QolamianPhysiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, IranMaliheh NobakhtDepartment of Histology and Neuroscience, Anti-microbial Resistance Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, IranJournal Article20181201<em><strong>Objective(s):</strong></em> Heart failure (HF) is one of the leading causes of death worldwide. Due to beneficial effects of stem cells, paracrine secretion of them has recently been used by researchers. The purpose of this study was to investigate the effects of intravenous injection (IV) of conditioned medium (CM) of human amniotic membrane-derived mesenchymal stem cell (MSC-CM) on HF.<br /><em><strong>Materials and Methods:</strong></em> Male Wistar rats (n=35, 180 g) were randomly divided into five groups: sham, HF, HF+MSC-CM, HF+culture medium and HF+phosphate-buffered saline (PBS). To induce HF, isoproterenol (170 mg/kg/d) was injected subcutaneously for 4 consecutive days. After 28 days, induction of HF was evaluated by echocardiography. A day after echocardiography, 50 μg culture medium/5 ml PBS in HF+culture medium group, 50 μg MSC-CM/5 ml PBS in HF+MSC-CM group and 5 ml PBS in HF+PBS group were injected two times for 4 successive days. The echocardiography was performed 4 weeks after the last injection of isoproterenol. To evaluate the fibrosis, morphology, and cardiac function, Trichrome Masson’s staining, Hematoxylin and Eosin staining and echocardiography were performed, respectively.<br /><em><strong>Results:</strong></em> CM significantly increased fractional shortening and ejection fraction, and also significantly decreased apoptotic nuclear condensation. Moreover, significant decreased level of fibrosis and increased level of angiogenesis was observed in the treatment group (P<0.05).<br /><em><strong>Conclusion:</strong></em> Our results indicated that IV injection of CM has therapeutic effects on HF by reducing fibrosis and preventing the progression of failure due to its paracrine effects.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Thalidomide attenuates the hyporesponsiveness of isolated atria to chronotropic stimulation in BDL rats: The involvement of TNF-α, IL-6 inhibition, and SOCS1 activation125912661388610.22038/ijbms.2019.32256.7742ENAli Hosseini-chegeniDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran0000-0001-5656-644XFarahnaz JazaeriDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran0000-0001-8392-9795Aliakbar Yousefi-AhmadipourDepartment of Laboratory of Sciences, Faculty of Paramedical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, IranMansour HeidariDepartment of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran0000-0002-6214-4638Alireza AbdollahiDepartment of Pathology, School of Medicine, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, IranAhmad Reza DehpourDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranExperimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran0000-0002-8001-5565Journal Article20180529<em><strong>Objective(s):</strong></em> Cirrhotic cardiomyopathy is a complication of uncured cirrhosis which is associated with hyporesponsiveness of the heart to sympathetic stimulation. The enhancement of portal pressure, nitric oxide (NO) level, pro-inflammatory mediators and down-regulation of Suppressor of Cytokine Signaling 1 (SOCS1) are involved in this situations. The present study seeks to examine the beneficial effect of thalidomide on cirrhotic cardiomyopathy. <br /><em><strong>Materials and Methods:</strong> </em>The male rats were grouped as: Sham/saline, Sham/Thalidomide, Bile Duct Ligation (BDL)/saline and BDL/Thalidomide. BDL model of cirrhosis was used. In the treatment groups, thalidomide (200 mg/kg/day) was administrated by intragastrial gavage for 28 consecutive days, the chronotropic response was assessed in isolated atria by isoproterenol stimulation. Serum levels of NO, IL-6 and TNF-α hepatic level were evaluated. The intrasplenic pulp pressure (ISPP) as the portal pressure and histopathologic assessment were assessed. Real time RT-PCR was used for the evaluation of SOCS1 gene expression.<br /><em><strong>Results:</strong></em> Our results showed that thalidomide administration could significantly increase the atrial chronotropic response in BDL animals. The increased level of portal pressure decreased by thalidomide in BDL animals. Thalidomide could ameliorate the histopathological conditions of BDL rats. Furthermore, the chronic treatment by this drug diminished the elevated levels of NO, TNF-α and IL-6 in BDL animals. On the other hand, hepatic SOCS1 expression was up-regulated by thalidomide treatment in this group. <br /><em><strong>Conclusion:</strong></em> Thalidomide improves the chronotropic hyporesponsiveness of isolated atria in BDL. This effect is probably mediated by the inhibiting NO, TNF-α and IL-6 production, reducing portal pressure and increasing the expression of SOCS1.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101The prevalence of exotoxins, adhesion, and biofilm-related genes in Staphylococcus aureus isolates from the main burn center of Tehran, Iran126712741393110.22038/ijbms.2019.34908.8291ENZahra MirMicrobial Biotechnology Research Center, Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0001-6405-7880Narges Nodeh FarahaniMicrobial Biotechnology Research Center, Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranSara AbbasianMicrobial Biotechnology Research Center, Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranFaranak AlinejadBurn Research Center, Shahid Motahari Hospital, Iran University of Medical Sciences, Tehran, IranMahboubeh SattarzadehBurn Research Center, Shahid Motahari Hospital, Iran University of Medical Sciences, Tehran, IranRamin PouriranSchool of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranMostafa DahmardeheiBurn Research Center, Shahid Motahari Hospital, Iran University of Medical Sciences, Tehran, IranMehdi MirzaiiSchool of Medicine, Shahroud University of Medical Sciences, Shahroud, IranSeyed Sajjad KhoramroozCellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, IranDavood Darban-SarokhalilMicrobial Biotechnology Research Center, Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0001-8081-3906Journal Article20180916<em><strong>Objective(s):</strong></em> The present study investigated the prevalence of genes encoding for exotoxins, adhesion and biofilm factors in Staphylococcus aureus isolates obtained from samples in a referral burn hospital in Tehran, Iran.<br /><em><strong>Materials and Methods:</strong></em> S. aureus isolates obtained from patients, personnel and surfaces in the wards of a burn hospital were identified and confirmed by biochemical and molecular tests, respectively. The susceptibility of isolates was determined using the disk diffusion method. Virulence factors were detected by multiplex PCR.<br /><em><strong>Results:</strong></em> The frequency of hla, hlb, hld, hlg, tst and pvl genes was 92.8%, 34.7%, 89.8%, 11.9%, 10.7%, and 0.5% respectively. The results revealed that the hla gene had the highest frequency among isolates (94.4% for methicillin-resistant S. aureus (MRSA) and 89.8% for methicillin-susceptible S. aureus (MSSA)). The most prevalent adhesion and biofilm-related gene was eno (85.6%). The prevalence of the remaining genes was as follows: fib (71.8%), clfB (70%), cna (59.2 %), fnbB (17.9%), icaA (72.4%), and icaD (85.6%). The incidence of fib, hlb, hlg, and tst genes was significantly higher in MRSA isolates compare to the MSSA isolates. Moreover, the resistance rates for all antibiotics were higher is MRSA isolates except for nitrofurantoin and chloramphenicol antibiotics.<br /><em><strong>Conclusion:</strong></em> Data indicate the high prevalence rates of virulence factors among S. aureus isolates, especially MRSA strains in the burn hospital. This should to be taken into account in the development of an effective infection control policy and continuous monitoring of drug resistance in hospitals.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Akt inhibitor deguelin aggravates inflammation and fibrosis in myocarditis127512821394910.22038/ijbms.2019.35518.8473ENShanshan LiDepartment of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China0000-0001-6443-958XYue WangDepartment of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaChunming ZhaoHuman anatomy and Histology and Embryology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaMeixiang ZhangDepartment of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaWei WangDepartment of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaXiaowei YuDepartment of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaJiao HuangDepartment of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaZhao WangDepartment of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, ChinaBo ZhuDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts 02118, USACheng Qian YinDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts 02118, USAHongxing CaiDepartment of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China0000-0002-6743-3922Journal Article20181013<em><strong>Objective(s):</strong></em> Myocarditis is characterized by inflammatory cell infiltration in myocardial stroma. Attenuation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β is a reliable mark for improving the prognosis. Protein kinase B (Akt) plays an important role in the development and progression of myocarditis. The specific role of the natural inhibitor of Akt, Deguelin, on myocarditis has not been reported. In this study, we used deguelin to investigate the effects of natural Akt inhibitor on myocarditis in experimental autoimmune myocarditis (EAM) rats.<br /><em><strong>Materials and Methods:</strong></em> EAM rat models were made by using Lewis rats and Deguelin was injected intraperitoneally on day 3, 6, 9, 12 and 15 after successful modeling. On day 18, rats were sacrificed and the heart weight (HW)/ body weight (BW) ratio were measured. The pathological changes, pathological scores and fibrosis area were evaluated after H.&E. and Masson’s trichrome staining. The mRNA levels of TNF-α and IL-1β were measured by RT-qPCR, while the protein expressions of TNF-α and IL-1β were detected by immunohistochemical staining and Western bolt. The protein expressions of Akt, Akt1, phosphorylated (p-) Akt and nuclear factor (NF)-κB were detected by Western bolt.<br /><em><strong>Results:</strong> </em>We found that the TNF-α and IL-1β levels, inflammatory scores and fibrosis areas were markedly increased after 18 days deguelin administration. <br /><em><strong>Conclusion:</strong></em> Akt inhibition with deguelin may aggravate myocarditis of EAM rats.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101WDR7 up-regulation upon knocking down of neighboring non-coding RNA using siRNAs encapsulated in polyamidoamine dendrimers128312871388110.22038/ijbms.2019.36135.8607ENSara KorStem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran0000-0002-3101-0194Vahid Erfani-MoghadamMedical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, IranDepartment of Medical Nanotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, IranReza SahebiDepartment of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran0000-0001-8702-0992Shabbou BahramianStem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran0000-0002-5529-3993Mohammad ShafieeStem Cell Research Center, Golestan University of Medical Sciences, Gorgan, IranDepartment of Medical Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran0000-0002-8931-1301Journal Article20181109<em><strong>Objective(s):</strong> </em>Breast cancer is the second leading cause of cancer death in females. Understanding molecular mechanisms in cancer cells compared with normal cells is crucial for diagnostic and therapeutic strategies. Long intergenic non-protein coding RNA, a regulator of reprogramming (lincRNA-RoR) is a noncoding RNA which initially was detected in induced pluripotent stem cells, and it has an important role in cell reprogramming and highly expressed in breast cancer cells. A key point in successful gene silencing is the usage of siRNA delivery system that is safe and efficient. <br /><em><strong>Materials and Methods:</strong></em> In this study, the fifth-generation of PAMAM dendrimer is used as a nanocarrier for entering siRNA molecules for gene silencing of lincRNA-RoR. WDR7 is the gene encoding adjacent of lincRNA-RoR, which has an important role in apoptosis and cell cycle. Gel retardation assay was used to find the best Negative/Positive (N/P) molar charge ratio of siRNA- PAMAM transfected into MDA-MB 231 cells. MTT assay was performed 24 hr after transfection revealed the IC50 value (half maximal inhibitory concentrations) about 100 nanomolar for lincRNA-ROR siRNA.<br /><em><strong>Results:</strong></em> The lincRNA-RoR and WDR7 gene expression changes were evaluated by real-time PCR after siRNA treatment and showed an increase in the gene expression of WDR7. <br /><em><strong>Conclusion:</strong></em> This study showed that PAMAM dendrimer G5/ siRNA could be a useful system delivery for future gene therapy approaches.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Metabolomics approach reveals urine biomarkers and pathways associated with the pathogenesis of lupus nephritis128812951393210.22038/ijbms.2019.38713.9178ENShiva KalantariChronic Kidney Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran-Iran0000-0001-7690-141XSaeed ChashmniamDepartment of Chemistry, Sharif University of Technology, Tehran, IranMohsen NafarUrology-Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0001-5636-2666Zahra ZakeriDepartment of Rheumatology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences Tehran, IranMahmoud ParvinDepartment of Pathology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences Tehran, IranJournal Article20190225<em><strong>Objective(s):</strong></em> lupus nephritis (LN) is a severe form of systemic lupus erythematosus (SLE) with renal complications. Current diagnosis is based on invasive renal biopsy and serum antibodies and complement levels that are not specific enough. The current study aims to identify new biomarker candidates for non-invasive diagnosis of LN and explore the pathogenic mechanisms that contribute to renal injury. <br /><em><strong>Materials and Methods:</strong></em> A metabolomics approach using 1H-nuclear magnetic resonance (1H-NMR), was developed for comparison of urine metabolic profile of 14 LN patients, 10 SLE patients, and 11 healthy controls (HCs). Differential biomarker candidates were identified by using multivariate modeling, and their diagnostic accuracy was evaluated by receiver operating characteristic analysis (ROC). <br /><em><strong>Results:</strong></em> Three metabolites were common in differentiating all three groups including beta-alanine, 2,2-dimethylsucssinic acid, and 3,4-Dihydroxyphenylacetaldehyde and suggested as a diagnostic panel for LN with AUC of 0.89, sensitivity of 81 %, and specificity of 100 %. Complementary analyses on pathways indicated that nicotinate and nicotinamide metabolism is the most important perturbed pathway in LN.<br /><em><strong>Conclusion:</strong></em> Metabolomics is a useful tool for identification of biomarkers with the ability to diagnose LN patients and predict perturbed pathways responsible for renal injury.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Reactive oxygen species mediate TNF-α-induced inflammatory response in bone marrow mesenchymal cells129613011388510.22038/ijbms.2019.37893.9006ENLiuzhong WuDepartment of Periodontics, School of Stomatology, China Medical University, Liaoning Province, ChinaDepartment of Periodontics, Shenyang Stomatological Hospital, Shenyang, Liaoning Province, China0000-0002-3718-5817Yaping PanDepartment of Periodontics, School of Stomatology, China Medical University, Liaoning Province, China0000-0001-6022-9665Journal Article20190122<em><strong>Objective(s):</strong></em> It is generally believed that the inflammatory response in bone marrow mesenchymal stem cells (BMSCs) transplantation leads to poor survival and unsatisfactory effects, and is mainly mediated by cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α). In this study, we explored the mechanisms underlying the TNF-α-induced inflammatory response in BMSCs.<br /> <em><strong>Materials and Methods:</strong></em> We treated BMSCs with TNF-α (1 and 10 ng/ml) for 5 days. The expression levels of key inflammatory mediators were evaluated by Real-time PCR. Intracellular ROS level was measured by using a 2, 7-dichlorofluorescein diacetate (DCF-DA).<br /><em><strong>Results:</strong></em> We found that TNF-α treatment dramatically increased the expression levels of some key inflammatory mediators, including IL-6, IL-1β, IFN-γ and transforming growth factor β (TGF-β). Moreover, TNF-α induced intracellular oxidative stress by elevating intracellular reactive oxygen species (ROS) level, which is due to the increase of lipid peroxidation, the reduction of antioxidant Glutathione (GSH) levels and the inhibition of many antioxidant enzyme activities in BMSCs. Interestingly, 5 µM curcumin, a ROS scavenger, dramatically lowered the TNF-α-induced inflammatory response in BMSCs. In addition, TNF-α induced the activation of extracellular-signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK), p38 and their down-stream transcription factors nuclear factor kappa B (NF-κB) pathway.<br /><em><strong>Conclusion:</strong></em> ROS mediated the TNF-α-induced inflammatory response via MAPK and NF-κB pathway, and may provide a novel strategy to prevent the inflammatory-dependent impairments in BMSCs.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Protection of BALB/c mice against pathogenic Brucella abortus and Brucella melitensis by vaccination with recombinant Omp16130213071393410.22038/ijbms.2019.36369.8665ENHamed AlizadehDepartment of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran0000000154463703Mehrooz DezfulianDepartment of Microbiology, Karaj Branch, Islamic Azad University, Karaj, IranMehdi RahnemaDepartment of Microbiology, Zanjan Branch, Islamic Azad University, Zanjan, IranJalil Fallah MehrabadiLister Laboratory of Microbiology, Tehran, IranDavood EsmaeiliDepartment of Microbiology and Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, IranApplied Virology ResearchCenter, Baqiyatallah University of Medical Sciences, Tehran, Iran0000-0001-9632-4058Journal Article20181120<em><strong>Objective(s):</strong></em> Prevention of the globally spread zoonotic infection, brucellosis which affects an extensive range of hosts is still challenging researchers. There are no approved vaccines for the prevention of human disease and those used for animal brucellosis have adverse properties, which limit their application. We investigated the immunological and protective effects of recombinant 16 kDa outer membrane protein of Brucella abortus (Omp16) which introduced a new candidate for brucellosis subunit vaccine. <br /><em><strong>Materials and Methods:</strong></em> Brucella Omp16 gene was cloned in pET-23a and expressed in Escherichia coli BL21 (DE3). Recombinant Omp16 (rOmp16) was purified using nickel resin and confirmed by Western blot analysis. BALB/c mice were immunized with rOmp16, afterward, specific serum antibodies and cytokine responses were evaluated. Protection of immunized mice against pathogenic B. abortus 544 and B. melitensis 16M was evaluated by the intraperitoneal bacterial challenge. <br /><em><strong>Results:</strong> </em>Sequencing results of the recombinant plasmid vector along with Western blotting confirmed the cloning procedure. Recognition of rOmp16 by specific IgG from serum samples of infected cases suggests the stimulation of immune response to this protein. Significant total serum IgG along with remarkable IgG1 and IgG2a response to the protein was recorded. A significant increase in IFN-γ, and IL-4 levels were observed from splenocyte cultures of immunized mice which were stimulated with rOmp16 suggesting the development of T-lymphocyte mediated immunity against the recombinant antigen. <br /><em><strong>Conclusion:</strong> </em>The intraperitoneal challenge with B. abortus 544 and B. melitensis 16M confirmed that rOmp16 is able to elicit efficient protective immune responses in the animal host.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Protein expression changes of HCN1 and HCN2 in hippocampal subregions of gerbils during the normal aging process130813131388310.22038/ijbms.2019.35760.8520ENChoong-Hyun LeeDepartment of Pharmacy, College of Pharmacy, Dankook University, Cheonan, Chungnam 31116, Republic of Korea0000-0001-5508-9004Joon Ha ParkDepartment of Anatomy, College of Korean Medicine, Dongguk University, Gyeongju, Gyeongbuk 38066, Republic of KoreaMoo-Ho WonDepartment of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea0000-0002-7178-6501Journal Article20181022<em><strong>Objective(s):</strong></em> Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play essential roles in various hippocampal functions, including regulation of long-term potentiation, synaptic plasticity, and hippocampal-dependent cognitive process. The objective of this study was to investigate age-related changes in HCN1 and HCN2 protein expressions in gerbil hippocampus at various ages. <br /><em><strong>Materials and Methods:</strong> </em>In this study, the protein expressions of HCN1 and HCN2 were compared in the hippocampus at the ages of 1, 3, 12, and 24 months using Western blot analysis and immunohistochemistry.<br /><em><strong>Results:</strong></em> Immunoreactivity of both HCN1 and HCN2 was shown primarily in cells of the pyramidal cell layer in the hippocampus proper and in cells of the granule cell layer in the dentate gyrus. HCN1 and HCN2 protein expression levels and immunoreactivity were significantly increased at three months (3 M) of age compared with those at 1 M of age. After that, both HCN1 and HCN2 expression levels in the hippocampus were gradually decreased with age. <br /><em><strong>Conclusion:</strong></em> Our results show that the normal aging process affects the expression levels of HCN1 and HCN2 in hippocampal cells in gerbils. There are marked reductions in HCN1 and HCN2 expressions in the aged hippocampus compared to the young hippocampus. Such reductions might be related to aging in the hippocampus.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Nitric oxide mediated the effects of nebivolol in cardiorenal syndrome131413241387910.22038/ijbms.2019.37400.8927ENGuldem MercanogluUniversity of Health Sciences, Faculty of Pharmacy, Department of Pharmacology, Istanbul-Turkey0000-0001-7594-7029Semen OnderIstanbul University, Istanbul Medical Faculty, Department of Pathology, Istanbul-Turkey0000-0002-1384-630XJournal Article20190109<em><strong>Objective(s):</strong> </em>Despite several proposed mechanisms for the pathophysiology of cardiorenal syndrome (CRS), the exact mechanism remains unclear. Nitrosative stress has been argued as a key mechanism recently. Nebivolol is a beta-blocker with nitric oxide (NO)-releasing effect. In the present study, NO-mediated effects of two different treatment regimes of nebivolol in CRS were studied. <br /><em><strong>Materials and Methods:</strong></em> Rats were divided into: sham-operated (sham-control), myocardial infarction (MI)-induced, (MI-control) early nebivolol-treated (MI-neb1) and late nebivolol-treated (Mı-neb2) groups. The effects of nebivolol were assessed both in the early and late period of MI by histologic, hemodynamic and biologic studies.<br /><strong><em>Results:</em></strong> Developed MI model was in line with the heart failure with preserved ejection fraction. Focal and total tubular damage findings were observed in MI-control group both in early and late period of MI. In parallel, subclinical functional damage was transformed into chronic renal dysfunction in this group. Increased inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) together with decreased neuronal NOS (nNOS) levels were in parallel with the increased inflammation and nitrosative stress biomarkers. Nebivolol effectively prevented both subclinical and clinical nephropathy. There was no statistical difference between the nebivolol treatment regimes.<br /><em><strong>Conclusion:</strong></em> The beneficial effects of nebivolol were closely related to the reduction of nitrosative damages as well as hemodynamic alterations. The NO-mediated effects were: prevention of nitrosative damage by decreasing iNOS, preservation of nNOS in order to maintain glomerular filtration rate (GFR), and restoration of eNOS in the late period of MI. On contrary to our previous work, early nebivolol administration had a similar effect with delayed administration of nebivolol on CRS.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Association of lipid markers with coronary heart disease and stroke mortality: A 15-year follow-up study132513301388410.22038/ijbms.2019.35617.8775ENBagher PahlavanzadeDepartments of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0002-4876-1058Farid ZayeriDepartments of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IranTaban BaghfalakiDepartments of Statistics, Faculty of Mathematical Sciences, Tarbiat Modares University, Tehran, IranOmid MozafariGolestan University of Medical Sciences, Gorgan, IranDavood KhaliliPrevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IranFereidoun AziziEndocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IranAlireza AbadiDepartment of Community Medicine, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0003-2653-6623Journal Article20181211<em><strong>Objective(s):</strong></em> It has been proposed that lipid markers may predict cardiovascular events; however, their effect may vary depending on the type of cardiovascular disease. The purpose of this study was to investigate the effects of lipid markers on death from coronary heart disease (CHD) and stroke in competing risks setting.<br /><em><strong>Materials and Methods:</strong></em> Participants included 2502 women and 2020 men, age 40 years or older from Tehran Lipid and Glucose Study. The association between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) with hazard and cumulative incidence of CHD and stroke was investigated using cause-specific hazard and sub-distribution hazard models. Statistical analyses were performed using “risk regression” and “cmprsk” package in R 3.3.2.<br /><em><strong>Results:</strong></em> One standard deviation (SD) increase in TC and LDL-C increased the hazard of CHD death by 1.42 (CI=1.07,1.89) and 1.41 (CI=1.04,1.93), respectively. 1-SD increase in TG increased the cumulative incidence of CHD death increased by 1.94 (CI=1.02,3.75) in women. Other risk factors were not associated with the hazard and cumulative incidence of CHD in women, men and the total sample. In addition, none of lipids had a significant effect on the hazard and cumulative incidence of stroke in men, women and the total sample.<br /><em><strong>Conclusion:</strong></em> The associations of lipid components on CHD death were modified by gender. TC, LDL-C and TG were independent predictors of CHD mortality in women. Furthermore, death due to stroke changes the association of lipid markers with CHD mortality.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Potential therapeutic effect of Moroccan propolis in hyperglycemia, dyslipidemia, and hepatorenal dysfunction in diabetic rats133113391393710.22038/ijbms.2019.33549.8004ENNawal El MenyiyLaboratory Physiology-Pharmacology & Environmental Health, Faculty of science Dhar El Mehraz, University Sidi Mohamed Ben Abdallah, Fez, Morocco0000-0002-4842-2056Noori Al-WailiNew York Medical Care for Nephrology, New York City, NY, USA0000-0002-4763-4444Asmae El GhouiziLaboratory Physiology-Pharmacology & Environmental Health, Faculty of science Dhar El Mehraz, University Sidi Mohamed Ben Abdallah, Fez, MoroccoSoukaina El-GuendouzLaboratory Physiology-Pharmacology & Environmental Health, Faculty of science Dhar El Mehraz, University Sidi Mohamed Ben Abdallah, Fez, MoroccoKhelod SalomNew York Medical Care for Nephrology, New York City, NY, USABadiaa LyoussiLaboratory Physiology-Pharmacology & Environmental Health, Faculty of science Dhar El Mehraz, University Sidi Mohamed Ben Abdallah, Fez, MoroccoJournal Article20180719<em><strong>Objective(s):</strong></em> The effect of propolis collected in Morocco on blood glucose, lipid profile, liver enzymes, and kidney function was investigated in control and diabetic rats. <br /><em><strong>Materials and Methods:</strong></em> Antioxidant activity of propolis was evaluated with the use of DPPH, 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS•+), ferric reducing power and total antioxidant activity assay. To study its effect in streptozotocin (STZ)-induced diabetes, the rats were divided into eight groups; four control and four diabetics. The animals received distilled water, glibenclamide, or propolis extract, 50 mg/kg/BW) or 100 mg/kg/b.wt, daily for 15 days. Blood glucose, triglyceride, lactic acid dehydrogenase, liver enzymes, creatinine, blood urea, lipid profile, and body weight were measured on day 15 after commencement of the treatment. <br /><em><strong>Results:</strong></em> Propolis has a strong antioxidant activity and high total flavonoids and polyphenols content. Glibenclamide and propolis have no significant effect on lipid parameters, and renal and hepatic function in non-diabetic rats. However, propolis or glibenclamide caused a significant lowering of blood glucose after a single administration and at day 15 after daily administration in diabetic rats (P<0.05). Both interventions significantly lowered lactic acid dehydrogenase, increased body weight, and ameliorated dyslipidemia and abnormal liver and kidney function caused by diabetes. The effect of propolis was dose-dependent and in a high dose it was more potent than glibenclamide. <br /><em><strong>Conclusion:</strong></em> Propolis exhibited strong antihyperglycemic, antihyperlipidemic, and hepato-renal protective effects in diabetes, and significantly lowered the elevated lactic acid dehydrogenase. The study demonstrated for the first-time the effect of Moroccan propolis in diabetes and it will pave the way for clinical investigations.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Eupafolin ameliorates lipopolysaccharide-induced cardiomyocyte autophagy via PI3K/AKT/mTOR signaling pathway134013461394810.22038/ijbms.2019.37748.8977ENYan GaoFunction Testing Lab, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi P.R. China0000-0002-0333-532XYi ZhangICU Department, Shaanxi Provincial People’s Hospital. Xi’an, Shaanxi P.R. ChinaYangyang FanObstetrical Department, Shaanxi Provincial People’s Hospital. Xi’an, Shaanxi P.R. ChinaJournal Article20190117<em><strong>Objective(s):</strong></em> Eupafolin, a major active component of Eupatorium perfoliatum L., has anti-inflammatory and anti-oxidant properties. Lipopolysaccharide (LPS) is responsible for myocardial depression. A line of evidences revealed that LPS induces autophagy in cardiomyocytes injury. This study aims to evaluate the effects of eupafolin on LPS-induced cardiomyocyte autophagy. <br /><em><strong>Materials and Methods:</strong></em> The effect of LPS on cell viability was examined by CCK-8. Autophagic protein 2 light chain 3 (LC3II), which was regulated by LPS and eupafolin, was examined using immunofluorescent staining. The expression levels of Beclin-1 and p62 were detected by western blotting. The effects of eupafolin on phosphatidylinositol-3-kinase/ protein kinase B/ mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway were also evaluated by western blotting and immunofluorescent staining. <br /><em><strong>Results:</strong></em> Eupafolin pretreatment reduced the expression of LC3II and Beclin-1, whereas p62 was significant increased. In addition, eupafolin promoted expression of PI3K/AKT/mTOR signaling pathway and mTOR inhibitor rapamycin reversed the inhibitory effects on LPS-induced cardiomyocyte autophagy. <br /><em><strong>Conclusion:</strong></em> Eupafolin exerts anti-autophagy activity via activation of PI3K/AKT/mTOR signaling pathway.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Contribution of potassium channels, beta2-adrenergic and histamine H1 receptors in the relaxant effect of baicalein on rat tracheal smooth muscle134713521393610.22038/ijbms.2019.36377.8666ENSaeideh SaadatNeurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-8588-7365Javad BoskabadiNeurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, IranMohammad Hossein BoskabadyNeurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran0000-0001-5736-9755Journal Article20181120<em><strong>Objective(s):</strong></em> Baicalein, a compound extracted from a variety of herbs, showed various pharmacological effects. This study evaluated the relaxant effects of baicalein and its underlying molecular mechanisms of action on rat’s isolated tracheal smooth muscle.<br /><em><strong>Materials and Methods:</strong></em> Tracheal smooth muscle were contracted by 10 μM methacholine or 60 mM KCl and the effects of cumulative concentrations of baicalein (5, 10, 20 and 40 mg/ml) and theophylline (0.2, 0.4, 0.6 and 0.8 mM) were evaluated. To examine the possible mechanism(s) of the relaxant effect of baicalein, its effect was also evaluated on incubated tissues with atropine, indomethacin, diltiazem, N(G)-Nitro-L-arginine methyl ester (L-NAME), glibenclamide, propranolol and chlorpheniramine.<br /><em><strong>Results:</strong></em> A concentration-dependent and significant relaxant effect was seen for baicalein in non-incubated tissues contracted by KCl or methacholine (P<em><strong>Conclusion:</strong></em> A potent relaxant effect comparable to the effect of theophylline was shown for baicalein, which was probably mediated via inhibition of histamine (H1) receptors, stimulation of beta2-adrenergic receptors and potassium channels activation.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Sodium valproate ameliorates aluminum-induced oxidative stress and apoptosis of PC12 cells135313581395010.22038/ijbms.2019.36930.8804ENForough IranpakDepartment of Biochemistry, Islamic Azad University of Shiraz, Shiraz, IranDiagnostic Laboratory Sciences and Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-4622-7476Jamileh SaberzadehDiagnostic Laboratory Sciences and Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-0912-9313Mahmood VesalDepartment of Biochemistry, Islamic Azad University of Shiraz, Shiraz, IranMohammad Ali TakhshidDiagnostic Laboratory Sciences and Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-0246-3765Journal Article20181217<em><strong>Objective(s):</strong> </em>According to recent studies, valproate shows some protection against oxidative stress (OS) induced by neurotoxins. Current investigation tried to determine the possible ameliorating effects of sodium valproate (SV) against aluminum (Al)-induced cell death, apoptosis, mitochondrial membrane potential (MMP), and OS in PC12 cells.<br /><em><strong>Materials and Methods:</strong></em> In this in vitro study, PC12 cells were treated with different concentrations of aluminum maltolate (Almal) with and without SV (50–400 µM). Cell viability was assessed by MTT assay. To measure quantitatively the effects of SV on Al-induced apoptosis and reactive oxygen species (ROS), flowcytometry using 7AAD/annexin-V and 2’, 7’-dichlorofluorescein diacetate staining were employed, respectively. MMP was monitored using the retention of rhodamine 123. Catalase (CAT) activity was assayed by the rate of decomposition of hydrogen peroxide. <br /><em><strong>Results:</strong> </em>Exposure of PC12 cells for 48 hr to Almal (125–2000 µM) significantly reduced cell viability (IC50=1090 μM), increased ROS generation and apoptosis, and reduced MMP and CAT activity. SV reduced the Almal-induced cell death and apoptosis. Furthermore, the effects of Almal on ROS generation, catalase activity, and MMP reduction were significantly diminished by SV. <br /><em><strong>Conclusion:</strong></em> Data from this study suggest that SV can inhibit Al-induced cell death and apoptosis of PC12 cells via ameliorating OS.Mashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-3866221120191101Renal histopathological and biochemical changes following adjuvant intervention of Momordica charantia and antiretroviral therapy in diabetic rats135913671388010.22038/ijbms.2019.31848.7663ENUgochukwu OfforDepartment of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South AfricaDepartment of Preclinical Sciences, School of Health Care Sciences, Faculty of Health Sciences, University of Limpopo, South Africa0000-0002-0805-229XEdwin Coleridge Stephen NaiduDepartment of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South Africa0000-0002-2691-4017Oluwatosin Olalekan OgedengbeDepartment of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South AfricaDepartment of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado Ekiti, NigeriaAyoola Isaac JegedeDepartment of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South AfricaDepartment of Basic Sciences, School of Medicine, Copperbelt University, ZambiaAniekan Imo PeterDepartment of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South AfricaDepartment of Anatomy, Faculty of Basic Medical Sciences, University of Uyo-Nigeria, Nigeria0000-0002-1155-6368Okpara Azu OnyemaechiDepartment of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South AfricaDepartment of Anatomy, School of Medicine, University of Namibia, Windhoek, NamibiaJournal Article20180514<em><strong>Objective(s):</strong></em> Diabetic nephropathy (DN) is an important primary cause of end-stage kidney disease. This study explores the mechanisms of the reno-protective effects of Momordica charantia (M. charantia) in diabetic rats following treatment with highly active antiretroviral therapy (HAART) regimen triplavar. <br /><em><strong>Materials and Methods:</strong></em> Adult male Sprague-Dawley rats (n=48) were divided into 7 groups (A-G).Treatment groups (B-G) had 7 animals per group and control group (Group A) had 6 animals per group. Diabetes was induced with streptozotocin (STZ) by intraperitoneal injection (STZ 45 mg/kg body weight). The animals were euthanized on the tenth week with kidneys removed for examination and blood obtained via cardiac puncture. <br /><em><strong>Results:</strong></em> Key renal parameters showed no albuminuria, normal blood urea nitrogen (BUN), serum creatinine and electrolytes in all groups treated with M. charantia. Untreated diabetic (Group B) and HAART treated diabetic (Group C) showed severe albuminuria, a significantly raised BUN and serum creatinine (P<0.05) and gross electrolyte disturbances. Blood glucose levels were consistently and significantly raised in all groups not receiving the adjuvant M. charantia (P<0.05). Levels of oxidative stress enzymes Superoxide dismutase (SOD), Catalase and activities of Reduced Gluthaione (GSH) and Malondiadehyde (MDA) were significantly lower in all groups not receiving M. charantia. Histopathology in untreated diabetic and HAART treated animals showed severe degenerative changes in the glomeruli and inflammatory cellular infiltration while M. charantia treated animals showed an essentially normal glomerular appearance with capillary loops and normal cytoarchitecture. <br /><em><strong>Conclusion:</strong></em> M. charantia extract administration improved blood glucose levels, reinstates renal function, reduces body weight loss and restores hyperglycemia.