Royan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501Xeno-Free Human Wharton’s Jelly Mesenchymal Stromal Cells Maintain Their Characteristic Properties after Long-Term Cryopreservation14515325070010.22074/cellj.2021.7131ENCaroline MathenOCT Therapies and Research, Pvt. Ltd., Mumbai, IndiaWilfrid DsouzaOCT Therapies and Research, Pvt. Ltd., Mumbai, IndiaJournal Article19700101<b>Objective</b><br/>The past decade has witnessed a rapid growth in harnessing the potential of adult stem cells for regenerative medicine. An investigational new drug (IND) or a regenerative medicine advanced therapy (RMAT) product must fulfil many requirements, such as stability studies, after cryopreservation. Such studies are important to ascertain the utility of off-the-shelf allogeneic cells for clinical applications. The present work describes a complete characterisation of xeno- free human Wharton’s Jelly mesenchymal stromal cells (hWJ-MSCs) before and up to 28 months post-cryopreservation. <br><b>Materials and Methods</b><br> In this experimental study, culture methods that involved plasma derived human serum and recombinant trypsin were used to develop clinical grade cells. Complete cell characterisation involved flow cytometry studies for viability, positive and negative markers, colony forming unit (CFU) potential, population doubling time (PDT), soft agar assay to evaluate in vitro tumourigenicity, karyotype analysis and differentiation studies which were performed before and at 6, 12, 18 and 28 months post-cryopreservation. <br><b>Results</b><br> Our data showed consistency in the flow cytometry, CFU assay, PDT, soft agar assay, karyotyping and differentiation studies. <br><b>Conclusion</b><br> Using our protocols for extended xeno-free culture and cryopreservation of hWJ-MSCs, we could establish the shelf life of the cell-based product for up to 28 months.https://www.celljournal.org/article_250700_84b76ac069e2aa8ace89da7024da8900.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501In Vitro Implantation Model Using Human Endometrial SUSD2+15416325070110.22074/cellj.2021.6979ENMarzieh Rahimipour.Department of Anatomy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranMina Jafarabadi.Reproductive Health Research Centre, Tehran University of Medical Sciences, Tehran, IranMojdeh Salehnia.Department of Anatomy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran0000-0001-7861-2232Journal Article19700101<strong>Objective</strong><br />This study evaluated a novel in vitro implantation model using human endometrial mesenchymal stem cells (EMSCs), SUSD2+, and myometrial smooth muscle cells (SMCs) that were co-cultured with mouse blastocysts as the surrogate embryo. <br /><strong>Materials and Methods</strong><br />In this experimental study, SUSD2+ MSCs were isolated from human endometrial cell suspensions (ECS) at the fourth passage by magnetic-activated cell sorting. The ECS and SUSD2+ cells were separately co-cultured with human myometrial muscle cells for five days. After collection of mouse blastocysts, the embryos were placed on top of the co-cultured cells for 48 hours. The interaction between the embryo and the cultured cells was assessed morphologically at the histological and ultrastructural levels, and by expression profiles of genes related to implantation. <br /><strong>Results</strong><br />Photomicrographs showed that trophoblastic cells grew around the embryonic cells and attached to theECS and SUSD2+ cells. Ultrastructural observations revealed pinopode and microvilli-like structures on the surfaces of both the ECS and SUSD2+ cells. Morphologically, the embryos developed to the egg-cylinder stage in both groups. Gene expression analysis showed no significant differences between the two groups in the presence of an embryo, but an increased expression of αV was detected in SUSD2+ cells compared to ECS cells in the absence of an embryo. <br /><strong>Conclusion</strong><br />This study showed that SUSD2+ cells co-cultured with SMCs could interact with mouse embryos. The co-cultured cells could potentially be used as an implantation model.https://www.celljournal.org/article_250701_24140fcffbcdb131ae235c6cdb1d0004.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501Alpha-Lipoic Acid Can Overcome The Reduced Developmental Competency Induced by Alcohol Toxicity during Ovine Oocyte Maturation16417325070210.22074/cellj.2021.7071ENAli Moghimi Khorasgani.Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology,
ACECR, Isfahan, Iran;.Department of Agricultural Biotechnology, College of Agriculture, Isfahan Univ0000-0002-1629-1901Reza Moradi.Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology,
ACECR, Isfahan, IranFarnoosh Jafarpour.Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology,
ACECR, Isfahan, IranFaezeh Ghazvinizadehgan.Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology,
ACECR, Isfahan, IranSomayyeh Ostadhosseini.Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology,
ACECR, Isfahan, IranAlireza Heydarnezhad.Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology,
ACECR, Isfahan, IranAli Akbar Fouladi-Nashta.Reproduction Genes and Development Group, Department of Veterinary Basic Sciences, The Royal Veterinary College, HawksheadLane
Hatfield, Herts AL97TA, UKJournal Article19700101<b>Objective</b><br/>Alpha-lipoic acid (ALA) as a strong antioxidant has a protective effect. This study was designed to assess whether supplementation of maturation medium with ALA during in vitro maturation (IVM) can attenuate the toxic effect of ethanol. <br><b>Materials and Methods</b><br> In this experimental study, to assess the antioxidant capacity of ALA challenged by 1% ethanol during in vitro maturation, immature ovine oocytes were exposed to 1% alcohol in the presence or absence of 25 µM ALA during oocyte maturation. The cumulus expansion index, intracellular reactive oxygen species (ROS), and thiol content levels were assessed in matured oocytes of various treatment groups. Consequently, the blastocyst formation rate of matured oocytes in various treatment groups were assessed. In addition, total cell number (TCN), cell allocation, DNA fragmentation, and relative gene expression of interested genes were assessed in resultant blastocysts. <br><b>Results</b><br> The results revealed that alcohol significantly reduced cumulus cells (CCs) expansion index and blastocyst yield and rate of apoptosis in resultant embryos. Addition of 25 µM ALA to 1% ethanol during oocyte maturation decreased ROS level and elevated Thiolcontent. Furthermore, supplementation of maturation medium with ALA attenuated the effect of 1% ethanol and significantly increased the blastocyst formation and hatching rate as compared to control and ethanol groups. In addition, the quality of blastocysts produced in ALA+ethanol was improved based on the low number of TUNEL positive cells, the increased expression level of mRNA for pluripotency, and anti-oxidant markers, and decreased expression of apoptotic genes. <br><b>Conclusion</b><br> The current findings demonstrate that ALA can diminish the effect of ethanol, possibly by decreasing the ROS level and increasing Thiolcontent during oocyte maturation. Using the ALA supplement may have implications in protecting oocytes from alcohol toxicity in affected patients.https://www.celljournal.org/article_250702_7f28e2ca74e63d5d3b33c44692cc8429.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501Metformin Reduces Vascular Assembly in High Glucose-Treated Human Microvascular Endothelial Cells in An AMPK-Independent Manner17418325070310.22074/cellj.2021.7212ENCarolina Silva.Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal;.i3S, Institute of Research and Innovation in Health, University of Porto, Porto, PortugalIlda Rodrigues.Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, PortugalSara Andrade.Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal;.i3S, Institute of Research and Innovation in Health, University of Porto, Porto, Portugal ;.IPATIMUP, InstituteRaquel Costa.Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal;.i3S, Institute of Research and Innovation in Health, University of Porto, Porto, PortugalRaquel Soares.Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal;.i3S, Institute of Research and Innovation in Health, University of Porto, Porto, PortugalJournal Article19700101<b>Objective</b><br/>The aim is to examine the effect of metformin in human microvascular endothelial cells exposed to high glucose (HG) concentration and compare them with the effects of other 5' adenosine monophosphate-activated protein kinase (AMPK) modulators under the same condition. <br><b>Materials and Methods</b><br> In this experimental study, human microvascular endothelial cells (HMECs) were treated with 15 mM metformin, 1 mM 5-aminoimidazol-4-carboxamideribonucleotide (AICAR) and 10 mM compound C in the presence of 20 mM glucose (hyperglycemic condition). Migration, invasion and proliferation were evaluated as well as the capillary-like structures formation. Moreover, the expression of angiogenic genes was assessed. <br><b>Results</b><br> Metformin significantly inhibited vessel formation and migration, although it did not change HMECs proliferation and invasion. In addition, metformin significantly reduced collagen formation as evidenced by histological staining. Concomitantly, expression of several genes implicated in angiogenesis and fibrosis, namely TGFß2, VEGFR2, ALK1, JAG1, TIMP2, SMAD5, SMAD6 and SMAD7, was slightly upregulated. Immunostaining for proteins involved in ALK5 receptor signaling, the alternative TGFß signaling pathway, revealed significant differences in SMAD2/3 expression. <br><b>Conclusion</b><br> Our data showed that metformin prevents vessel assembly in HMECs, probably through an AMPK- independent mechanism. Understanding the molecular mechanisms by which this pharmacological agent affects endothelial dysfunction is of paramount importance and paves the way to its particular use in preventing development of diabetic retinopathy and nephropathy, two processes where angiogenesis is exacerbated.https://www.celljournal.org/article_250703_1b60a81ee9d155b9b0ed36e799ead5f8.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501Cardioprotective Effect of Quercetin against Ischemia/Reperfusion Injury Is Mediated Through NO System and Mitochondrial K-ATP Channels18419025102310.22074/cellj.2021.7183ENYing LiuThe Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaYi SongThe Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaSiyuan LiThe Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaLi MoThe Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaJournal Article20220310<strong><span dir="ltr" style="left: 118.11px; top: 400.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.09886);" role="presentation">Objective:</span><span dir="ltr" style="left: 190.635px; top: 400.383px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span></strong><span dir="ltr" style="left: 195.443px; top: 400.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.01033);" role="presentation">Quercetin (Que) is a plant-derived polyphenolic compound, that was shown to possess anti-inflammatory </span><span dir="ltr" style="left: 118.11px; top: 415.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.988768);" role="presentation">activity in myocardial ischemia/reperfusion (I/R) models</span><span dir="ltr" style="left: 483.954px; top: 415.383px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 487.944px; top: 415.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.988605);" role="presentation">in vivo</span><span dir="ltr" style="left: 530.454px; top: 415.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.990162);" role="presentation">; however, detailed mechanisms of its anti-inflammatory </span><span dir="ltr" style="left: 118.11px; top: 430.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.02414);" role="presentation">effects remain unclear. This study aimed to examine the effects of quercetin postconditioning (QPC) on I/R-induced </span><span dir="ltr" style="left: 118.11px; top: 445.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.01277);" role="presentation">inflammatory response in a rat model and evaluate the role of the mitochondrial K-ATP (mitoK</span><span dir="ltr" style="left: 753.119px; top: 454.965px; font-size: 8.745px; font-family: sans-serif; transform: scaleX(1.09068);" role="presentation">ATP</span><span dir="ltr" style="left: 769.478px; top: 445.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.042);" role="presentation">) channels and NO </span><span dir="ltr" style="left: 118.103px; top: 460.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.0255);" role="presentation">system in this regard.</span><br role="presentation" /><strong><span dir="ltr" style="left: 118.103px; top: 486.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.08489);" role="presentation">Materials and Methods:</span></strong><span dir="ltr" style="left: 286.26px; top: 486.213px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 291.165px; top: 486.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.02623);" role="presentation">In this experimental study, hearts of male Wistar rats (250 ± 20 g) perused by Langendorff </span><span dir="ltr" style="left: 118.103px; top: 501.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.00646);" role="presentation">apparatus, were subjected to 30 minutes of global ischemia followed by 55 minutes reperfusion, and Que was added </span><span dir="ltr" style="left: 118.103px; top: 516.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.01633);" role="presentation">to the perfusion solution immediately at the onset of reperfusion. Creatine kinase (CK) levels in the coronary effluent </span><span dir="ltr" style="left: 118.103px; top: 531.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.01105);" role="presentation">were measured by spectrophotometry. Interleukin-1 (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) levels were </span><span dir="ltr" style="left: 118.103px; top: 546.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.02435);" role="presentation">analyzed by an enzyme-linked immunosorbent assay (ELISA) rat specific kit to assess the inflammatory condition of </span><span dir="ltr" style="left: 118.103px; top: 561.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.01434);" role="presentation">the myocardial tissue.</span><br role="presentation" /><strong><span dir="ltr" style="left: 118.103px; top: 587.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.20765);" role="presentation">Results:</span></strong><span dir="ltr" style="left: 177.278px; top: 587.043px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 180.908px; top: 587.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.00945);" role="presentation">Our results showed that QPC significantly improved left ventricular developed pressure (LVDP) (P<0.05), and </span><span dir="ltr" style="left: 118.103px; top: 602.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.04354);" role="presentation">decreased the CK release into the coronary effluent vs. control group (P<0.01). The levels of IL-1β (P<0.01), TNF-α </span><span dir="ltr" style="left: 118.103px; top: 617.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.00713);" role="presentation">(P<0.01), and IL-6 (P<0.05) were significantly diminished in Que-treated groups when compared to the control group. </span><span dir="ltr" style="left: 118.103px; top: 632.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.953846);" role="presentation">Inhibiting mitoK</span><span dir="ltr" style="left: 220.164px; top: 632.043px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 220.175px; top: 641.632px; font-size: 8.745px; font-family: sans-serif; transform: scaleX(1.09068);" role="presentation">ATP</span><span dir="ltr" style="left: 236.535px; top: 641.632px; font-size: 8.745px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 240.211px; top: 632.05px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.00522);" role="presentation">channels by 100 μM 5-hydroxydecanoate and blocking NO system by 100 μM L-NAME reversed the </span><span dir="ltr" style="left: 118.108px; top: 647.05px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.992067);" role="presentation">cardioprotective effects of Que.</span><br role="presentation" /><strong><span dir="ltr" style="left: 118.108px; top: 672.88px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.1556);" role="presentation">Conclusion:</span></strong><span dir="ltr" style="left: 204.778px; top: 672.88px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 209.977px; top: 672.88px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.03249);" role="presentation">The findings of this study suggested that QPC exerts cardioprotective effects on myocardial I/R injury </span><span dir="ltr" style="left: 118.108px; top: 687.88px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.981756);" role="presentation">(MIRI) through inhibition of inflammatory reactions and improvement of contractility potential. Also, mitoKATP channels </span><span dir="ltr" style="left: 118.108px; top: 702.88px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.98759);" role="presentation">and NO system might be involved in this anti-inflammatory effect</span>https://www.celljournal.org/article_251023_f7392da94c7c28daed92b8f320cf7168.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501Anti-Atherosclerotic Effect of Afrocyclamin A against Vascular Smooth Muscle Cells Is Mediated via p38 MAPK Signaling Pathway191198251024ENYan GuDepartment of Vascular Surgery, Tianjin First Center Hospital, Tianjin, ChinaZhanzhan XiaoDepartment of Emergency Services, The Fourth People’s Hospital of Jinan City, Jinan, Shandong Province, ChinaJianlie WuDepartment of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao City, ChinaMingjin GuoDepartment of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao City, ChinaPing LvDepartment of Hematology, The Fourth People’s Hospital of Jinan City, Jinan, Shandong Province, ChinaNing DouDepartment of General Surgery, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, ChinaJournal Article20220310<strong><span dir="ltr" style="left: 118.11px; top: 440.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.09886);" role="presentation">Objective:</span></strong><span dir="ltr" style="left: 190.635px; top: 440.383px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 195.632px; top: 440.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.02183);" role="presentation">Research suggests that fine particulate matter (PM2.5) contributes to the expansion and development of </span><span dir="ltr" style="left: 118.11px; top: 455.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.993023);" role="presentation">atherosclerosis. Infiltration and proliferation of vascular smooth muscle cells (VSMCs) from the blood vessel media into </span><span dir="ltr" style="left: 118.11px; top: 470.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.00324);" role="presentation">the intima, is an important step in the atherosclerosis pathophysiology. Afrocyclamin A, is an oleanane-type triterpene </span><span dir="ltr" style="left: 118.11px; top: 485.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.991419);" role="presentation">saponin, isolated from</span><span dir="ltr" style="left: 264.84px; top: 485.383px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 270.225px; top: 485.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.00793);" role="presentation">Androsace umbellate</span><span dir="ltr" style="left: 412.343px; top: 485.383px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 414.795px; top: 485.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.0542);" role="presentation">, which is commonly used in Chinese herbal medicine. In the study, we </span><span dir="ltr" style="left: 118.11px; top: 500.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.998086);" role="presentation">examined the effect of Afrocyclamin A on PM2.5-induced VSMCs proliferation and scrutinized possible mechanisms of </span><span dir="ltr" style="left: 118.11px; top: 515.383px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.00432);" role="presentation">action.</span><br role="presentation" /><strong><span dir="ltr" style="left: 118.11px; top: 541.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.08044);" role="presentation">Materials and Methods:</span></strong><span dir="ltr" style="left: 285.578px; top: 541.213px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 290.138px; top: 541.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.02722);" role="presentation">In the experimental study, counting Kit-8 (CCK-8) assay was used for estimation of VSMCs </span><span dir="ltr" style="left: 118.11px; top: 556.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.979295);" role="presentation">viability. BrdU immunofluorescence was used for estimation of VSMCs proliferation. The levels of antioxidant parameters </span><span dir="ltr" style="left: 118.11px; top: 571.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.01236);" role="presentation">such as malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH); proinflammatory cytokines such </span><span dir="ltr" style="left: 118.11px; top: 586.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.04493);" role="presentation">as interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nitric oxide (NO), endothelin-1 (ET-1), and vascular </span><span dir="ltr" style="left: 118.11px; top: 601.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.01446);" role="presentation">cell adhesion molecule-1 (VCAM-1), were estimated. The expression of proliferating cell nuclear antigen (PCNA) and </span><span dir="ltr" style="left: 118.11px; top: 616.213px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.03694);" role="presentation">phospho-p38 MAPK (p-p38 MAPK) was assessed.</span><br role="presentation" /><strong><span dir="ltr" style="left: 118.11px; top: 642.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.20765);" role="presentation">Results:</span></strong><span dir="ltr" style="left: 177.285px; top: 642.043px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span><span dir="ltr" style="left: 181.875px; top: 642.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.0067);" role="presentation">Compared to PM2.5-treated cells, in addition to reducing PM2.5-induced VSMCs proliferation, Afrocyclamin </span><span dir="ltr" style="left: 118.11px; top: 657.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.03111);" role="presentation">A reduced the expression of PCNA and p-p38 MAPK, down-regulated the level of TNF-α, IL-1β, IL-6, VCAM-1, MDA </span><span dir="ltr" style="left: 118.11px; top: 672.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.01629);" role="presentation">and ET-1, and up-regulated SOD, GSH and NO level. Furthermore, the anti-proliferative effect of Afrocyclamin A was </span><span dir="ltr" style="left: 118.11px; top: 687.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.999999);" role="presentation">considerably increased following co-incubation of Afrocyclamin A with SB203580 (p38 MAPK inhibitor) in comparison </span><span dir="ltr" style="left: 118.11px; top: 702.043px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.983146);" role="presentation">with Afrocyclamin A-treated cells.</span><br role="presentation" /><strong><span dir="ltr" style="left: 118.11px; top: 727.873px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.1556);" role="presentation">Conclusion:</span><span dir="ltr" style="left: 204.78px; top: 727.873px; font-size: 15px; font-family: sans-serif;" role="presentation"> </span></strong><span dir="ltr" style="left: 212.505px; top: 727.873px; font-size: 15px; font-family: sans-serif; transform: scaleX(1.0909);" role="presentation">Based on the results, we can conclude that Afrocyclamin A might reduce PM2.5-induced VSMCs </span><span dir="ltr" style="left: 118.11px; top: 742.873px; font-size: 15px; font-family: sans-serif; transform: scaleX(0.991312);" role="presentation">proliferation via reduction of p38 MAPK signaling pathway.</span>https://www.celljournal.org/article_251024_9f9180de61fce03926a5081dc5b92784.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501miR-373 Suppresses Cell Proliferation and Apoptosis via Regulation of SIRT1/PGC-1α/NRF2 Axis in Pancreatic Cancer19921025070510.22074/cellj.2021.7038ENQing-Hua YinDepartment of Hepatobiliary Surgery, The First Hospital of Changsha, Changsha 410000, P.R.ChinaYuan ZhouDepartment of Hepatobiliary Surgery, The First Hospital of Changsha, Changsha 410000, P.R.ChinaZhi-Yuan LiDepartment of Gastrointestinal Surgery, The Central Hospital of Hengyang City, Hengyang 421001, P.R.ChinaJournal Article19700101<b>Objective</b><br/>Our study aimed to investigate function and mechanism of miR-373 in proliferation and apoptosis of pancreatic cancer (PC) cells by regulating NAD+-dependent histone deacetylase sirtulin 1 (SIRT1). <br><b>Materials and Methods</b><br> This experimental study included two PC cell lines AsPC-1 and PANC-1 in which expression levels of miR-373 and SIRT1 were manipulated. The level of miR-373 was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) method. Expression levels of SIRT1, BCL-2, BAX, cleaved CASPASE-8/9/3, PARP, PGC-1α, NRF2, eNOS and iNOS were examined via RT-qPCR and western blotting, respectively. The binding sites of miR-373 on the SIRT1 were examined via dual-luciferase assay. Cell proliferation and apoptosis were examined by MTT assay, colony formation assay, Annexin-V/PI staining and TUNEL assay. The oxidative metabolic changes were monitored by reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) detection. <br><b>Results</b><br> miR-373 could specifically target the 3’-UTR of SIRT1 and reduce its expression in PC cells. Either elevated expression of miR-373 or partial loss of SIRT1 inhibited cell proliferation and induced cell apoptosis. Accumulation of BAX and cleaved CASPASE-8/9/3, inhibition of PGC-1α/NRF2 pathway, increase oxidative stress and reduction of BCL-2 as well as uncleaved PARP were found in the presence of miR-373 or the absence of SIRT1. Overexpression of SIRT1 could reduce anti-proliferative and pro-apoptotic effects of miR-373. <br><b>Conclusion</b><br> Overall, this study concluded that miR-373-dependent SIRT1 inhibition displays anti-proliferative and pro- apoptotic roles in PC cells via PGC-1α/NRF2 pathway, which highlights miR-373 as a potential target for PC treatment.https://www.celljournal.org/article_250705_8cf67575985e3ee3f6ba5326aacce97c.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501Identification of Circulating hsa-miR-324-3p and hsa-miR-331-3p Exchanges in The Serum of Alzheimer’s Patients and Insights into The Pathophysiological Pathways21121725070610.22074/cellj.2021.7047ENMaryam HeydariZohreh Hojati0000-0003-4831-0123Moein DehbashiJournal Article19700101<strong>Objective</strong><br />Alzheimer’s disease (AD) is a type of dementia. Currently, there are not any existing and reliable methods for the prognosis or diagnosis of AD. Hence, finding a diagnostic/prognostic biomarker for AD helps physicians to prescribe the treatments and methods preventing disease progression. Circulating microRNAs (miRNAs) are the most promising biomarkers due to their non-invasive and easily accessible for diagnosis and prognosis of AD. The aim of current study is to evaluate expression levels of two unwell-known circulating miRNAs including hsa-miR-324-3p and hsa-miR-331-3p in serums of AD patients and to understand their roles in AD physiopathogenesis by in silico analysis. <br /><strong>Materials and Methods</strong><br />In this case and control study, to get the gene targets related to these two miRNAs, TargetScan, miRTargetLink Human and mirDIP web servers were applied. In addition, gene networks and gene ontology enrichment analysis were performed by STRING 10.5, KEGG and ShinyGO v0.41. Experimentally, expression levels of these two miRNAs in the serum of 21 patients with AD and 23 healthy individuals were compared using the quantitative reverse transcription polymerase chain reaction (qRT-PCR) method. <br /><strong>Results</strong><br />The pathophysiological pathways associated with these two miRNAs were nucleotide metabolism and cellular response to stress pathway. Furthermore, the upregulated expression levels of hsa-miR-324-3p and hsa-miR-331-3p in comparison with the healthy control serums were not statistically significant (P > 0.05). <br /><strong>Conclusion</strong><br />Non-significant results were obtained from the expression levels of AD patients and two significant pathways were obtained by networks and gene enrichment analysis.https://www.celljournal.org/article_250706_aa939928ddc9e40b0dbd6b20ca6f5f82.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501Circ-RNA Expression Pattern and circ-RNA-miRNA-mRNA Network in The Pathogenesis of Human Intervertebral Disc Degeneration21822425070710.22074/cellj.2021.6832ENZhiliang GuoDepartment of Orthopedic, No. 89 Hospital of Chinese PLA, Weifang, 261021, ChinaYuanyuan LiuStomatology Medical College, Weifang Medical University, Weifang 261053, Shandong, ChinaYu GaoClinical Medical College, Weifang Medical University, Weifang 261053, Shandong, ChinaXiumei GuanClinical Medical College, Weifang Medical University, Weifang 261053, Shandong, ChinaHong LiClinical Medical College, Weifang Medical University, Weifang 261053, Shandong, ChinaMin ChengClinical Medical College, Weifang Medical University, Weifang 261053, Shandong, ChinaJournal Article19700101<b>Objective</b><br/>The present study aimed to screen the differentially expressed (DE) circular RNAs (circ-RNAs) between lumbar intervertebral disc degeneration (IVDD) and normal tissues. Material and Methods In this experimental study, microarray hybridization was performed to evaluate circ-RNA expression, and the DE circ-RNAs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Host genes of DE circ-RNAs were predicted, and their functions were evaluated. Further, a competitive endogenesis (ce) RNA network among 4 DE circ-RNAs-miRNA-mRNA was constructed by Cytoscape. <br><b>Results</b><br> A total of 2636 circ-RNAs were detected in all samples; among them, 89.23% were exonic circ-RNAs. There were 138 DE circ-RNAs, including 134 up-regulated circ-RNAs and 4 downregulated circ-RNAs in IVDD samples. qRT-PCR validation experiments showed that expression trends of hsa_circ_0003239, hsa_circ_0003162, hsa_circ_0005918, and hsa_circ_0005556 were in line with the microarray analysis results. Functional enrichment analysis showed that host genes of DE circ-RNAs significantly disturbed pathways of regulation of actin cytoskeleton, propanoate metabolism, and ErbB signaling pathway. The four DE circ-RNAs related ceRNA network was constructed. Conclusions Our results revealed that circ-RNAs can function as miRNA sponges and regulate parent gene expression to affect IVDD.https://www.celljournal.org/article_250707_db3384269ee981be853f96462b93b237.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501Metastasis Inhibition by Cell Type Specific Expression of BRMS1 Gene under The Regulation of miR200 Family Response Elements22523725070810.22074/cellj.2021.6988ENSamila Farokhimanesh.Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;.Department of Biotechnology, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University,Mahdi Forouzandeh Moghadam.Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranMarzieh Ebrahimi.Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and
Technology, ACECR, Tehran, Iran0000-0003-1140-0379Zahra Sadat Hashemi4.Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences,
Tehran, IranJournal Article19700101<b>Objective</b><br/>Specific expression of therapeutic genes in cancer therapy has been per used for many years. One of the innovative strategies that have recently been introduced is employing miRNA response elements (MREs) of microRNAs (whose expression are reduced or inhibited in cancerous cells) into the 3´UTR of the therapeutic genes for their specific expression. Accordingly, MREs of anti-metastatic miRNA family have been used in 3´UTR of the metastasis suppressor gene in the corresponding cells to evaluate the level of metastatic behavior. Material and Methods In this experimental study, 3´UTR of the ZEB1 gene with 592 bp length, encompassing multiple MREs of miR-141, miR-429, miR-200b and miR-200c, was employed to replace BRMS1 3´UTR. The obtained vector was then assessed in the context of MCF-10A, MDA-MB231 and MCF-7 cells. <br><b>Results</b><br> It was shown that the employed MREs are able to up-regulate BRMS expression in the metastatic MDA- MB231 cells (almost 3.5-fold increase), while it was significantly reduced within tumorigenic/non-metastatic MCF-7 cells. Specific expression of BRMS1 in metastatic cells led to a significant reduction in their migratory and invasive characteristics (about 65% and 55%, respectively). Two-tailed student’s t test was utilized for statistical analysis. <br><b>Conclusion</b><br> It was demonstrated that a chimeric vector containing BRMS1 which is regulated by miR-200 family response element may represent a promising therapeutic tool. This is due to the capability of the chimeric vector for cell type-specific expression of anti-metastatic genes with lowest side-effects. It consequently prohibits the invasive characteristics of metastatic cells.https://www.celljournal.org/article_250708_509a8dea3514c7233ae496a8c66bbd07.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501Bibliometric Analysis of Global Circular RNA Research Trends from 2007 to 201823824625070910.22074/cellj.2021.7143ENRan Wu.Department of Pharmacy, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaFei Guo.Department of Transfusion Medicine, Changhai Hospital, Second Military Medical University, Shanghai, ChinaChen Wang.Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, ChinaBaohua Qian.Department of Transfusion Medicine, Changhai Hospital, Second Military Medical University, Shanghai, ChinaFuming Shen.Department of Pharmacy, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaFang Huang.Department of Pharmacy, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaJournal Article19700101<strong>Objective</strong><br />Circular RNA (circRNA) is of significant interest in genetic research. The aim of this study was to assess global trends in circRNA research production in order to shed new light on future research frontiers. <br /><strong>Materials and Methods</strong><br />In this retrospective study, we conducted a literature search using the Web of Science Core Collection (WoSCC) database on March 21, 2019 to retrieve publications from 2007 to 2018. Excel 2013, CiteSpace V, and VOSviewer were used to evaluate bibliometric features that included publication output, countries/regions, institutions, journals, citation frequency, H-index, and research hotspots. <br /><strong>Results</strong><br />Global cumulative publication output on circRNA consisted of 998 papers with a total citation of 28 595 during 2007-2018. China, the US, and Germany were the most prolific countries. China ranked first in H-index (60 times) and citations (13 333 times). The most productive institution was Nanjing Medical University with 73 papers. Biochemical and Biophysical Research Communications (impact factor [IF]2017:2.559) ranked first among journals in the number of publications (64 papers). The keywords shifted from "sequence", "intron", and "splice-site" to "transcriptome", "microRNA sponge", "exon circularization", and "circRNA biogenesis" overtime. The burst keywords "transcriptome", "microRNA sponge", "exon circularization", and "circRNA biogenesis" were the latest frontiers by 2018. <br /><strong>Conclusion</strong><br />This is a relatively novel bibliometric analysis to inspect research related to circRNA. The results show that publications have continuously increased in the past decade. China, the US, and Germany were the leading countries/regions in terms of quantity. Recent studies on topics related to circRNA biogenesis and function should be closely followed in this field.https://www.celljournal.org/article_250709_a9d097bb4579867de8b4dfa8ee5a00a0.pdfRoyan Institute, Iranian Academic Center for Education Culture and Research (ACECR)Cell Journal (Yakhteh)2228-580623220210501Is There any Alternative Receptor for SARS-CoV-2?24725025071010.22074/cellj.2021.7977ENMahtab Shahriari FelordiDepartment of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR,
Tehran, IranArash MemarnejadianSernova Corp., London, Ontario, CanadaMustapha NajimiLaboratory of Pediatric Hepatology and Cell Therapy, Institute of Experimental and Clinical Research (IREC), Université Catholique de
Louvain, Brussels, Belgium0000-0002-7329-9635Journal Article19700101Angiotensin-converting enzyme II (ACE2) in association with type II transmembrane serine protease (TMPRSS2) is considered the main receptor of SARS-CoV-2. However, considering the clinical complications of COVID-19 in different organs, there is no strong association between the abundance of ACE2/TMPRSS2 co-expression and clinical features of the disease and the severity of complications. Since SARS-CoV-2 affects certain organs that lack or have low expression of ACE2/TMPRSS2, it may be possible that the virus employs other receptors for colonization and entry. Based on recent studies, glucose-regulated protein 78 (GRP78) can be a potential alternative receptor for SARS-CoV-2 entry. In this letter, supporting evidence proposed GRP78 as an alternative receptor in SARS-CoV-2 infection.https://www.celljournal.org/article_250710_ba986739e3fbddbee18c72d0aa20d68e.pdf