Triple-Gene Therapy for Stroke: A Proof-of-Concept in Vivo Study in Rats.

Abstract:

:Natural brain repair after stroke is extremely limited, and current therapeutic options are even more scarce with no clinical break-through in sight. Despite restricted regeneration in the central nervous system, we have previously proved that human umbilical cord blood mono-nuclear cells (UCB-MC) transduced with adenoviral vectors carrying genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) successfully rescued neurons in amyotrophic lateral sclerosis and spinal cord injury. This proof-of-principle project was aimed at evaluating the beneficial effects of the same triple-gene approach in stroke. Rats subjected to distal occlusion of the middle cerebral artery were treated intrathecally with a combination of these genes either directly or using our cell-based (UCB-MC) approach. Various techniques and markers were employed to evaluate brain injury and subsequent recovery after treatment. Brain repair was most prominent when therapeutic genes were delivered via adenoviral vector- or UCB-MC-mediated approach. Remodeling of brain cortex in the stroke area was confirmed by reduction of infarct volume and attenuated neural cell death, depletion of astrocytes and microglial cells, and increase in the number of oligodendroglial cells and synaptic proteins expression. These results imply that intrathecal injection of genetically engineered UCB-MC over-expressing therapeutic molecules (VEGF, GDNF, and NCAM) following cerebral blood vessel occlusion might represent a novel avenue for future research into treating stroke.

journal_name

Front Pharmacol

authors

Sokolov ME,Bashirov FV,Markosyan VA,Povysheva TV,Fadeev FO,Izmailov AA,Kuztetsov MS,Safiullov ZZ,Shmarov MM,Naroditskyi BS,Palotás A,Islamov RR

doi

10.3389/fphar.2018.00111

subject

Has Abstract

pub_date

2018-02-15 00:00:00

pages

111

issn

1663-9812

journal_volume

9

pub_type

杂志文章
  • Individualized Dosing With High Inter-Occasion Variability Is Correctly Handled With Model-Informed Precision Dosing-Using Rifampicin as an Example.

    abstract::Rifampicin exhibits complexities in its pharmacokinetics (PK), including high inter-occasion variability (IOV), which is challenging for dose individualization. Model-informed precision dosing (MIPD) can be used to optimize individual doses. In this simulation-based study we investigated the magnitude of IOV in rifamp...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00794

    authors: Keutzer L,Simonsson USH

    更新日期:2020-05-27 00:00:00

  • Role of Calcitonin Gene-Related Peptide in Nociceptive Modulationin Anterior Cingulate Cortex of Naïve Rats and Rats With Inflammatory Pain.

    abstract::It is known that calcitonin gene-related peptide (CGRP) plays a key role in pain modulation in the brain. There are high expressions of CGRP and CGRP receptor in anterior cingulate cortex (ACC), an important brain structure in pain modulation. The present study explored the role and mechanisms of CGRP and CGRP recepto...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00928

    authors: Hou KS,Wang LL,Wang HB,Fu FH,Yu LC

    更新日期:2020-06-26 00:00:00

  • Recent Progress in CFTR Interactome Mapping and Its Importance for Cystic Fibrosis.

    abstract::Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride channel found in secretory epithelia with a plethora of known interacting proteins. Mutations in the CFTR gene cause cystic fibrosis (CF), a disease that leads to progressive respiratory illness and other complications of phenotypic variance resu...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2017.00997

    authors: Lim SH,Legere EA,Snider J,Stagljar I

    更新日期:2018-01-17 00:00:00

  • Non-linear Entropy Analysis in EEG to Predict Treatment Response to Repetitive Transcranial Magnetic Stimulation in Depression.

    abstract::Background: Biomarkers that predict clinical outcomes in depression are essential for increasing the precision of treatments and clinical outcomes. The electroencephalogram (EEG) is a non-invasive neurophysiological test that has promise as a biomarker sensitive to treatment effects. The aim of our study was to invest...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.01188

    authors: Shalbaf R,Brenner C,Pang C,Blumberger DM,Downar J,Daskalakis ZJ,Tham J,Lam RW,Farzan F,Vila-Rodriguez F

    更新日期:2018-10-30 00:00:00

  • Ubc9 Attenuates Myocardial Ischemic Injury Through Accelerating Autophagic Flux.

    abstract:Aims:SUMOylation is a post-translational modification that plays a crucial role in the cellular stress response. We aimed to demonstrate whether and how the SUMO E2 conjugation enzyme Ubc9 affects acute myocardial ischemic (MI) injury. Methods and Results:Adenovirus expressing Ubc9 was administrated by multipoint inje...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.561306

    authors: Xiao Q,Chen XH,Jiang RC,Chen SY,Chen KF,Zhu X,Zhang XL,Huang JJ,Qin Y,Zhang GP,Yi Q,Luo JD

    更新日期:2020-09-15 00:00:00

  • Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents against Hormone-Dependent Breast Cancer Cells.

    abstract::Most breast and prostate tumors are hormone-dependent, making it possible to use hormone therapy in patients with these tumors. The design of effective endocrine drugs that block the growth of tumors and have no severe side effects is a challenge. Thereupon, synthetic steroids are promising therapeutic drugs for the t...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2017.00979

    authors: Scherbakov AM,Komkov AV,Komendantova AS,Yastrebova MA,Andreeva OE,Shirinian VZ,Hajra A,Zavarzin IV,Volkova YA

    更新日期:2018-01-10 00:00:00

  • Hydroxypropyl-β-Cyclodextrin Complexes of Styryllactones Enhance the Anti-Tumor Effect in SW1116 Cell Line.

    abstract::Styryllactones, a class of compounds obtained from the genus Goniothalamus (Annonaceae), have demonstrated in vitro antitumor activity. However, the aqueous solubility of these compounds is poor. In this study, we identified the absolute configurations of the previously isolated compounds, which were first isolated in...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00484

    authors: Ma R,Chen JT,Ji XY,Xu XL,Mu Q

    更新日期:2020-04-22 00:00:00

  • 8-Formylophiopogonanone B Antagonizes Paraquat-Induced Hepatotoxicity by Suppressing Oxidative Stress.

    abstract::Flavonoids are some of the most important natural products with a variety of physiological activities. 8-Formylophiopogonanone B (8-FOB) is a naturally existing homoisoflavonoid in Ophiopogon japonicus. Paraquat (PQ) has been widely used as a potent herbicide and has high toxicity in humans. The goal of the present st...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.01283

    authors: Qian JY,Deng P,Liang YD,Pang L,Wu LC,Yang LL,Zhou Z,Yu ZP

    更新日期:2019-10-24 00:00:00

  • Corrigendum: Furanodiene Induces Extrinsic and Intrinsic Apoptosis in Doxorubicin-Resistant MCF-7 Breast Cancer Cells via NF-κB-Independent Mechanism.

    abstract::[This corrects the article on p. 648 in vol. 8, PMID: 28959205.]. ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,已发布勘误

    doi:10.3389/fphar.2017.00934

    authors: Zhong ZF,Yu HB,Wang CM,Qiang WA,Wang SP,Zhang JM,Yu H,Cui L,Wu T,Li DQ,Wang YT

    更新日期:2017-12-18 00:00:00

  • Key Clinical Interest Outcomes of Pharmaceutical Administration for Veterans With Post-Traumatic Stress Disorder Based on Pooled Evidences of 36 Randomised Controlled Trials With 2,331 Adults.

    abstract::Background: The effects of drug treatment on veterans, who have a high risk of post-traumatic stress disorder (PTSD), are not clear, and the guidelines are different from the recommendations of the recent meta-analysis. Our goal was to find the efficacy and frequencies of complications of drugs that can treat PTSD in ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2020.602447

    authors: Zhao YF,Huang ZD,Gu HY,Guo GL,Yuan RX,Zhang C

    更新日期:2020-12-17 00:00:00

  • Visceral Fat Dysfunctions in the Rat Social Isolation Model of Psychosis.

    abstract::Medication with neuroleptics has been associated with adipose tissue dysfunctions and, in particular, with increased visceral fat amount. However, several studies suggested that antipsychotic treatment might not be the main responsible of fat mass accumulation, as this has been also described in not treated psychotic ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2017.00787

    authors: Schiavone S,Camerino GM,Mhillaj E,Zotti M,Colaianna M,De Giorgi A,Trotta A,Cantatore FP,Conte E,Bove M,Tucci P,Morgese MG,Trabace L

    更新日期:2017-11-08 00:00:00

  • MetMaxStruct: A Tversky-Similarity-Based Strategy for Analysing the (Sub)Structural Similarities of Drugs and Endogenous Metabolites.

    abstract:BACKGROUND:Previous studies compared the molecular similarity of marketed drugs and endogenous human metabolites (endogenites), using a series of fingerprint-type encodings, variously ranked and clustered using the Tanimoto (Jaccard) similarity coefficient (TS). Because this gives equal weight to all parts of the encod...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2016.00266

    authors: O'Hagan S,Kell DB

    更新日期:2016-08-22 00:00:00

  • Doxorubicin Induces Endotheliotoxicity and Mitochondrial Dysfunction via ROS/eNOS/NO Pathway.

    abstract::Background: Doxorubicin (Dox) can induce endotheliotoxicity and damage the vascular endothelium (VE). The most principle mechanism might be excess reactive oxygen species (ROS) generation. Nevertheless, the characteristics of ROS generation, downstream mechanisms, and target organelles in Dox-induced endotheliotoxicit...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.01531

    authors: He H,Wang L,Qiao Y,Zhou Q,Li H,Chen S,Yin D,Huang Q,He M

    更新日期:2020-01-10 00:00:00

  • Impact of Biologic Treatment of Crohn's Disease on the Rate of Surgeries and Other Healthcare Resources: An Analysis of a Nationwide Database From Poland.

    abstract::Background: There is conflicting evidence on the impact of biologic treatment on the rate of complications and surgeries in Crohn's disease (CD). We aimed to assess real-world consequences of biologic treatment of CD. Methods: All adult patients with CD treated with infliximab and adalimumab in the years 2012-2014 wer...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00621

    authors: Holko P,Kawalec P,Pilc A

    更新日期:2018-06-11 00:00:00

  • Serotonin, neural markers, and memory.

    abstract::Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly under...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2015.00143

    authors: Meneses A

    更新日期:2015-07-21 00:00:00

  • A New Framework to Implement Model-Informed Dosing in Clinical Guidelines: Piperacillin and Amikacin as Proof of Concept.

    abstract::Background: Modeling and simulation is increasingly used to study pediatric pharmacokinetics, but clinical implementation of age-appropriate doses lags behind. Therefore, we aimed to develop model-informed doses using published pharmacokinetic data and a decision framework to adjust dosing guidelines based on these do...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.592204

    authors: Hartman SJF,Swaving JGE,van Beek SW,van Groen BD,de Hoop M,van der Zanden TM,Ter Heine R,de Wildt SN

    更新日期:2020-12-16 00:00:00

  • Risk of Upper Gastrointestinal Bleeding in a Cohort of New Users of Low-Dose ASA for Secondary Prevention of Cardiovascular Outcomes.

    abstract::The Health Improvement Network UK primary care database was used to identify a cohort of 38 077 individuals aged 50-84 years with a first prescription of low-dose acetylsalicylic acid (ASA; 75-300 mg/day) for secondary prevention of cardiovascular or cerebrovascular events during 2000-2007. From this cohort, 169 incid...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2010.00126

    authors: Cea Soriano L,Rodríguez LA

    更新日期:2010-10-14 00:00:00

  • Ontological and Non-Ontological Resources for Associating Medical Dictionary for Regulatory Activities Terms to SNOMED Clinical Terms With Semantic Properties.

    abstract::Background: Formal definitions allow selecting terms (e.g., identifying all terms related to "Infectious disease" using the query "has causative agent organism") and terminological reasoning (e.g., "hepatitis B" is a "hepatitis" and is an "infectious disease"). However, the standard international terminology Medical D...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.00975

    authors: Bousquet C,Souvignet J,Sadou É,Jaulent MC,Declerck G

    更新日期:2019-09-10 00:00:00

  • A Non-imaging High Throughput Approach to Chemical Library Screening at the Unmodified Adenosine-A3 Receptor in Living Cells.

    abstract::Recent advances in fluorescent ligand technology have enabled the study of G protein-coupled receptors in their native environment without the need for genetic modification such as addition of N-terminal fluorescent or bioluminescent tags. Here, we have used a non-imaging plate reader (PHERAstar FS) to monitor the bin...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2017.00908

    authors: Arruda MA,Stoddart LA,Gherbi K,Briddon SJ,Kellam B,Hill SJ

    更新日期:2017-12-13 00:00:00

  • The Selective SIK2 Inhibitor ARN-3236 Produces Strong Antidepressant-Like Efficacy in Mice via the Hippocampal CRTC1-CREB-BDNF Pathway.

    abstract::Depression is a widespread chronic medical illness affecting thoughts, mood, and physical health. However, the limited and delayed therapeutic efficacy of monoaminergic drugs has led to intensive research efforts to develop novel antidepressants. ARN-3236 is the first potent and selective inhibitor of salt-inducible k...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.624429

    authors: Liu Y,Tang W,Ji C,Gu J,Chen Y,Huang J,Zhao X,Sun Y,Wang C,Guan W,Liu J,Jiang B

    更新日期:2021-01-14 00:00:00

  • Baicalin induced dendritic cell apoptosis in vitro.

    abstract::This study was aimed to investigate the effects of baicalin (BA), a major flavonoid constituent found in the herb Baikal skullcap, on dendritic cells (DCs). DCs were generated by culturing murine bone marrow (BM) cells for 6 days with granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4, and lipopol...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,收录出版

    doi:10.3389/fphar.2011.00015

    authors: Zhang H,Jiao Q,Gong Q,Zhang Y,Zhang W,Hu Z

    更新日期:2011-03-29 00:00:00

  • Hippocampal Hyperactivity as a Druggable Circuit-Level Origin of Aberrant Salience in Schizophrenia.

    abstract::The development of current neuroleptics was largely aiming to decrease excessive dopaminergic signaling in the striatum. However, the notion that abnormal dopamine creates psychotic symptoms by causing an aberrant assignment of salience that drives maladaptive learning chronically during disease development suggests a...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章,评审

    doi:10.3389/fphar.2020.486811

    authors: Kätzel D,Wolff AR,Bygrave AM,Bannerman DM

    更新日期:2020-10-16 00:00:00

  • Heme oxygenase induction attenuates TNF-α-induced hypertension in pregnant rodents.

    abstract::Pre-eclampsia is a hypertensive disorder of pregnancy initiated by placental insufficiency and chronic ischemia. In response, several pathways activated in the placenta are responsible for the maternal syndrome, including increased production of the anti-angiogenic protein, sFlt-1, and inflammatory cytokines, especial...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2015.00165

    authors: George EM,Stout JM,Stec DE,Granger JP

    更新日期:2015-08-17 00:00:00

  • Functional Study of Novel Bartter's Syndrome Mutations in ClC-Kb and Rescue by the Accessory Subunit Barttin Toward Personalized Medicine.

    abstract::Type III and IV Bartter syndromes (BS) are rare kidney tubulopathies caused by loss-of-function mutations in the CLCNKB and BSND genes coding respectively for the ClC-Kb chloride channels and accessory subunit barttin. ClC-K channels are expressed in the Henle's loop, distal convoluted tubule, and cortical collecting ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.00327

    authors: Sahbani D,Strumbo B,Tedeschi S,Conte E,Camerino GM,Benetti E,Montini G,Aceto G,Procino G,Imbrici P,Liantonio A

    更新日期:2020-03-17 00:00:00

  • The Management of Heavy Menstrual Bleeding After Percutaneous Coronary Intervention in a Woman of Reproductive Age.

    abstract::Heavy menstrual bleeding (HMB), previously known as menorrhagia, is in place with heavy flow and longer lasting days of bleeding during menstrual period, sequentially leading to anemia. We reported a rare case of HMB in a 33-year-old patient after percutaneous coronary intervention (PCI), who presented with acute coro...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.01573

    authors: Gu ZC,Shi FH,Zhu J,Wan F,Shen L,Li H

    更新日期:2019-01-15 00:00:00

  • Mapping Evidence of Pharmacy Services for COVID-19 in China.

    abstract:Objective:To explore the role of pharmacists and innovation of pharmacy interventions for COVID-19 patients in China. Methods:We comprehensively searched PubMed and Chinese databases Sinomed, China National Knowledge Infrastructure to identify articles reporting pharmacist interventions and pharmacy services for COVID...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2020.555753

    authors: Yi ZM,Hu Y,Wang GR,Zhao RS

    更新日期:2020-10-02 00:00:00

  • A Comprehensive Strategy to Evaluate Compatible Stability of Chinese Medicine Injection and Infusion Solutions Based on Chemical Analysis and Bioactivity Assay.

    abstract::Stability of traditional Chinese medicine injection (TCMI) is an important issue related with its clinical application. TCMI is composed of multi-components, therefore, when evaluating TCMI stability, several marker compounds cannot represent global components or biological activities of TCMI. Till now, when evaluatin...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2017.00833

    authors: Li JP,Liu Y,Guo JM,Shang EX,Zhu ZH,Zhu KY,Tang YP,Zhao BC,Tang ZS,Duan JA

    更新日期:2017-11-15 00:00:00

  • Lithraea caustic (Litre) Extract Promotes an Antitumor Response Against B16 Melanoma.

    abstract::Melanoma immunotherapy, specifically the autotransplant of dendritic cells charged with tumors antigens, has shown promising results in clinical trials. The positive clinical effects of this therapy have been associated to increased Th17 response and delayed-type hypersensitivity (DTH) against to tumor antigens. Some ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2019.01201

    authors: Robles-Planells C,Michelson SA,Mena J,Escrig D,Rojas JL,Sanchez-Guerrero G,Hernández R,Barrera-Avalos C,Rojo LE,Sauma D,Kalergis AM,Imarai M,Fernández R,Robles CA,Leiva-Salcedo E,Santander R,Escobar A,Acuña-Castillo C

    更新日期:2019-10-22 00:00:00

  • Icariin, but Not Genistein, Exerts Osteogenic and Anti-apoptotic Effects in Osteoblastic Cells by Selective Activation of Non-genomic ERα Signaling.

    abstract::Genistein and icariin are flavonoid compounds that exhibit estrogen-like properties in inducing bone formation and reducing bone loss associated with estrogen deficiency in both preclinical and clinical studies. However, the mechanisms that are involved in mediating their estrogenic actions in bone cells are far from ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2018.00474

    authors: Ho MX,Poon CC,Wong KC,Qiu ZC,Wong MS

    更新日期:2018-05-11 00:00:00

  • GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells.

    abstract::Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABAA receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability ...

    journal_title:Frontiers in pharmacology

    pub_type: 杂志文章

    doi:10.3389/fphar.2017.00089

    authors: Filatova E,Kasian A,Kolomin T,Rybalkina E,Alieva A,Andreeva L,Limborska S,Myasoedov N,Pavlova G,Slominsky P,Shadrina M

    更新日期:2017-02-28 00:00:00