Expression of Dominant Negative K6W-Ubiquitin in the Lens Epithelium via an Adenoviral Vector Delays Posterior Capsule Opacification in a Rabbit Model.

Abstract:

PURPOSE:Ubiquitin is involved in cell proliferation and differentiation, and the objective of this study is to investigate the potential of dominant negative Ubiquitin (Ub) with a lysine to tryptophan mutation at the 6 position (K6W) through an adenoviral expression vector in the prevention of posterior capsule opacification (PCO) in a rabbit PCO model. METHODS:Recombinant dominant negative K6W-Ub adenovirus (RAd-K6W-Ub) with green fluorescent protein (RAd-K6W-Ub/GFP) and RAd-GFP viruses (control) were generated with QBI-HEK 293A cells. New Zealand rabbits receiving lens phacoemulsification were given an intraoperative anterior chamber injection of the viruses. The images of anterior segment photography taken by a slit lamp biomicroscopy were analyzed by posterior capsule opacification manual software (POCOman) for PCO grading. The intraocular pressure (IOP) was detected with a non-contact tonometer (NCT). The expression of α-smooth muscle actin (α-SMA) was assessed by Western blotting. Cell migration ability in cultured rabbit's lens epithelial cells (LECs) was evaluated by scratch healing assay. RESULTS:The expression of GFP and Ub in the lens epithelium was markedly upregulated after 48 hours vector injection. Eyes injected with RAd-K6W-Ub showed a significantly lower PCO degree compared with controls. Meanwhile, higher IOP and corneal edema was observed in groups with a higher RAd-K6W-Ub virus dosage. The expression of α-SMA was down-regulated in the RAd-K6W-Ub eyes as compared to controls at the 15th day after injection. Cell migration was inhibited by RAd-K6W-Ub infection. CONCLUSIONS:RAd-K6W-Ub at an appropriate dosage could inhibit the proliferation of LECs and the formation of PCO in rabbit models. However, a higher dosage of Rad- K6W-Ub viral vector caused toxic effects to the surrounding tissues, such as corneal edema and high IOP.

journal_name

Curr Mol Med

authors

Bao X,Hou M,Peng R,Luo F,Wu M

doi

10.2174/1566524017666170331163751

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

160-168

issue

2

eissn

1566-5240

issn

1875-5666

pii

CMM-EPUB-82605

journal_volume

17

pub_type

杂志文章
  • Immune tolerance elicited via unique ocular and oral routes.

    abstract::Immune tolerance can be induced by numerous methods. This review article aims to draw lines of similarity and contrast between two unique models of immune tolerance, namely Anterior Chamber Associated Immune Deviation (ACAID) and Nickel-induced oral tolerance. ACAID is an immune tolerance model that leads to the gener...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524015666150114114602

    authors: Ashour HM

    更新日期:2015-01-01 00:00:00

  • Antisense strategies.

    abstract::Antisense technology exploits oligonucleotide analogs to bind to target RNAs via Watson-Crick by hybridization. Once bound, the antisense agent either disables or induces the degradation of the target RNA. Antisense agents may also be used to alter splicing. Developing antisense technology involves the creation of a n...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524043360375

    authors: Crooke ST

    更新日期:2004-08-01 00:00:00

  • Molecular genetic approaches for studying the etiology of diabetic nephropathy.

    abstract::A critical challenge faced by clinical nephrologists today is the escalating number of patients developing end stage renal disease, a major proportion of which is attributed to diabetic nephropathy (DN). The need for new measures to prevent and treat this disease cannot be overemphasized. To this end, modern genetic a...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524054553504

    authors: Ng DP,Krolewski AS

    更新日期:2005-08-01 00:00:00

  • LTP, memory and structural plasticity.

    abstract::Our current understanding of the mechanisms of information processing and storage in the brain, based on the concept proposed more than fifty years ago by D. Hebb, is that a key role is played by changes in synaptic efficacy induced by coincident pre- and postsynaptic activity. Decades of studies of the properties of ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524023362041

    authors: Muller D,Nikonenko I,Jourdain P,Alberi S

    更新日期:2002-11-01 00:00:00

  • Selective Inhibition of SIRT2 Improves Outcomes in a Lethal Septic Model.

    abstract:BACKGROUND:Seven isoforms of histone deacetylase Class III have been reported - Sirtuin (SIRT) 1-7. We recently demonstrated that EX-527, an inhibitor of SIRT1, reduces mortality in a mouse model of lethal-cecal-ligationand- puncture (CLP)-induced septic shock. Our present study was aimed at determining whether selecti...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/156652401507150903185852

    authors: Zhao T,Alam HB,Liu B,Bronson RT,Nikolian VC,Wu E,Chong W,Li Y

    更新日期:2015-01-01 00:00:00

  • Inhibition of autophagy strengthens celastrol-induced apoptosis in human pancreatic cancer in vitro and in vivo models.

    abstract:OBJECTIVES:Celastrol, a quinone methide triterpenoid, could induce apoptosis in pancreatic cancer cells. The purpose of this study is to determine whether there is protective autophagy after celastrol treatment in pancreatic cancer cells and the synergistic effects of celastrol and 3-MA in vitro and in vivo. METHODS:T...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524014666140414211223

    authors: Zhao X,Gao S,Ren H,Huang H,Ji W,Hao J

    更新日期:2014-05-01 00:00:00

  • Molecular mechanisms of tumor invasion and metastasis: an integrated view.

    abstract::As tumors progress to increased malignancy, cells within them develop the ability to invade into surrounding normal tissues and through tissue boundaries to form new growths (metastases) at sites distinct from the primary tumor. The molecular mechanisms involved in this process are incompletely understood but those as...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524033479447

    authors: Cairns RA,Khokha R,Hill RP

    更新日期:2003-11-01 00:00:00

  • p38 MAP kinase interacts with and stabilizes pancreatic and duodenal homeobox-1.

    abstract::Pancreatic and duodenal homeobox-1 (PDX-1) is a homeodomain-containing transcription factor that plays a critical role in pancreatic development, β-cell differentiation, maintenance of normal β-cell function and tumorigenesis. PDX-1 is subjected to extensive post-translational modifications for its stability, subcellu...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Zhou G,Wang H,Liu SH,Shahi KM,Lin X,Wu J,Feng XH,Qin J,Tan TH,Brunicardi FC

    更新日期:2013-03-01 00:00:00

  • Entosis and Related Forms of Cell Death within Cells.

    abstract::By eliminating the unneeded or mutant cells, programmed cell death actively participates in a wide range of biological processes from embryonic development to homeostasis maintenance in adult. Continuing efforts have identified multiple cell death pathways, with apoptosis, necrosis and autophage the mostly studied. Re...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524015666151026100339

    authors: Wang Y,Wang XD

    更新日期:2015-01-01 00:00:00

  • Clinical laboratory testing in human medicine based on the detection of glycoconjugates.

    abstract::The purpose of this review is to provide a concise overview of developments over the last 15 years in the field of laboratory tests in human medicine that are based on the detection of alterations in the glycan part of glycoconjugates. We show how glycosylation-based diagnostic testing is widespread in the current cli...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652407780831629

    authors: Schulz BL,Laroy W,Callewaert N

    更新日期:2007-06-01 00:00:00

  • Ipsilateral hippocampal proteomics reveals mitochondrial antioxidative stress impairment in cortical-lesioned chronic mild stressed rats.

    abstract::In this study, a two-dimensional gel-based proteomic approach was applied to profile the protein alterations underlying the significant adverse effects from post-stroke depression (PSD). In view of the close association between left prefrontal cortical dysfunction and PSD, a PSD rat model was constructed through a lef...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524014666141021143333

    authors: Pan J,Liu H,Zhou J,Liu Z,Yang Y,Peng Y,You H,Yang D,Xie P

    更新日期:2014-01-01 00:00:00

  • Eicosanoids in asthma, allergic inflammation, and host defense.

    abstract::Eicosanoids are diverse mediators of inflammation that derive from a single cell membrane phospholipid-associated precursor, arachidonic acid. This precursor is metabolized to several groups of lipid mediators, including (but not limited to) prostaglandins, leukotrienes, and lipoxins, in a tightly regulated, coordinat...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652408785160989

    authors: Boyce JA

    更新日期:2008-08-01 00:00:00

  • Molecular Investigations of the Newly Synthesized Azomethines as Antioxidants: Theoretical and Experimental Studies.

    abstract:BACKGROUND:In this study, the antioxidant property of new synthesized azomethins has been investigated as theoretical and experimental. METHODS AND RESULTS:Density functional theory (DFT) was employed to investigate the Bond Dissociation Enthalpy (BDE), Mulliken Charges, NBO analysis, Ionization Potential (IP), Electr...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524019666190509102620

    authors: Shahab S,Sheikhi M,Filippovich L,Dikusar E,Pazniak A,Rouhani M,Kumar R

    更新日期:2019-01-01 00:00:00

  • Interaction of tgf-beta with immune cells in airway disease.

    abstract::Asthma, chronic obstructive pulmonary disorder (COPD), and cystic fibrosis (CF), chronic diseases of the airways, are characterized by symptoms such as inflammation of the lung tissue, mucus hypersecretion, constriction of the airways, and excessive fibrosis of airway tissue. Transforming growth factor (TGF)-beta, a c...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652408785160943

    authors: Moore B,Murphy RF,Agrawal DK

    更新日期:2008-08-01 00:00:00

  • Bitter gourd (Momordica charantia) is a cornucopia of health: a review of its credited antidiabetic, anti-HIV, and antitumor properties.

    abstract::Bitter gourd (Momordica charantia, BG) is both a nutritious and healthy food with a distinctive bitter flavor, and it is also widely exploited in folklore medicine. This review focuses on the efficacies and molecular mechanisms of BG-induced anti-diabetic, anti-HIV, and antitumor activities contributed by over twenty ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652411795976583

    authors: Fang EF,Ng TB

    更新日期:2011-07-01 00:00:00

  • The many faces of glutathione transferase pi.

    abstract::Glutathione transferase Pi (GST-pi, GSTP) is known to strongly affect human susceptibility to several cancers, asthma and neurodegenerative disorders. As with other glutathione transferases, it catalyses the addition of reduced glutathione to electrophilic species, and it is important in metabolite detoxification. It ...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652411794859278

    authors: Vasieva O

    更新日期:2011-03-01 00:00:00

  • Induction of anti-chlamydial mucosal immunity by transcutaneous immunization is enhanced by topical application of GM-CSF.

    abstract::Transcutaneous immunization (TCI) involves the direct application of antigen plus adjuvant to skin, taking advantage of the large numbers of Langerhans cells and other resident skin dendritic cells, that process antigen then migrate to draining lymph nodes where immune responses are initiated. We have used this form o...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524054863906

    authors: Hickey DK,Bao S,Ikeda LT,Carey AJ,Beagley KW

    更新日期:2005-09-01 00:00:00

  • Ursodeoxycholic Acid (UDCA) Promotes Lactate Metabolism in Mouse Hepatocytes through Cholic Acid (CA) - Farnesoid X Receptor (FXR) Pathway.

    abstract:BACKGROUND:Persistent hyperlactatemia is associated with greater mortality in shock. Liver is the main site of lactate metabolism. METHOD:In the first part, freshly isolated hepatocytes were incubated in 10% fetal bovine serum William's E medium supplemented with 10 mM lactate. Cells were then exposed to 100 μM ursode...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524020666200123161340

    authors: Wang L,He HW,Zhou X,Long Y

    更新日期:2020-01-01 00:00:00

  • Involvement of Upregulated P53-Induced Death Domain Protein in Retinal Ganglion Cells Apoptosis After Optic Nerve Crush.

    abstract:PURPOSE:Retinal ganglion cells (RGCs) apoptosis is a common characteristic of optic neuropathies. p53-induced protein with a death domain (PIDD) is a well-known regulator of genotoxic stress-induced apoptosis, which is constitutively cleaved into three main fragments: PIDD-N, PIDD-C and PIDD-CC. Thus, we aim to determi...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524019666190918160032

    authors: Zhang M,Chen L,Xu F,Jiang L,Yan W,Kunwar B,Tang F,Yang K,Shen C,Huang H,Lv J,Qin C,Wu X,Zeng S,Li M,Zhong S,Chen Q

    更新日期:2019-01-01 00:00:00

  • The quest for surrogate markers of angiogenesis: a paradigm for translational research in tumor angiogenesis and anti-angiogenesis trials.

    abstract::Inhibition of tumor angiogenesis suppresses tumor growth and metastatic spreading in many experimental models, suggesting that anti-angiogenic drugs may be used to treat human cancer. During the past decade more than eighty molecules that showed anti-angiogenic activity in preclinical studies were tested in clinical c...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524033479410

    authors: Rüegg C,Meuwly JY,Driscoll R,Werffeli P,Zaman K,Stupp R

    更新日期:2003-12-01 00:00:00

  • Elevated Interleukin 37 Expression Associated With Disease Activity in HLA-B27 Associated Anterior Uveitis and Idiopathic Anterior Uveitis.

    abstract:BACKGROUND & OBJECTIVE:Interleukin 37 (IL-37) is an important regulator of the anti-inflammatory T-cell response. In this study, we investigated its expression and function in peripheral blood mononuclear cells (PBMCs) of patients with HLA-B27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS:15 pati...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524018666180207152941

    authors: Zhao B,Zhang S,Chen W,Zhang R,Jiang R,Zhang R,Chen L

    更新日期:2018-03-09 00:00:00

  • The Bromodomain and Extra-Terminal Protein Inhibitor OTX015 Suppresses T Helper Cell Proliferation and Differentiation.

    abstract:BACKGROUND:Dynamic epigenetic alterations accompanying CD4+ T helper cell differentiation have been implicated in multiple autoimmune diseases. The bromodomain and extra-terminal (BET) proteins are epigenetic regulators that recognize and bind to acetylated histones in chromatin and are targets for pharmacological inhi...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524019666190126112238

    authors: Hu X,Schewitz-Bowers LP,Lait PJP,Copland DA,Stimpson ML,Li JJ,Liu Y,Dick AD,Lee RWJ,Wei L

    更新日期:2018-01-01 00:00:00

  • Hydroxycitric Acid Inhibits Renal Calcium Oxalate Deposition by Reducing Oxidative Stress and Inflammation.

    abstract:OBJECTIVE:The study aimed to evaluate the preventive effects of hydroxycitric acid(HCA) for stone formation in the glyoxylate-induced mouse model. MATERIALS AND METHODS:Male C57BL/6J mice were divided into a control group, glyoxylate(GOX) 100 mg/kg group, a GOX+HCA 100 mg/kg group, and a GOX+HCA 200 mg/kg group. Blood...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524020666200103141116

    authors: Liu X,Yuan P,Sun X,Chen Z

    更新日期:2020-01-01 00:00:00

  • Prolylcarboxypeptidase independently activates plasma prekallikrein (fletcher factor).

    abstract::Prolylcarboxypeptidase isoform 1 (PRCP1) is capable of regulating numerous autocrines and hormones, such as angiotensin II, angiotensin III, αMSH1-13, and DesArg(9) bradykinin. It does so by cleaving a C-terminal PRO-X bond. Recent work also indicates that the human PRCP1 activates plasma prekallikrein (PK) to kallikr...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524014666141015153519

    authors: Wang J,Matafonov A,Madkhali H,Mahdi F,Watson D,Schmaier AH,Gailani D,Shariat-Madar Z

    更新日期:2014-01-01 00:00:00

  • RAGE as a receptor of HMGB1 (Amphoterin): roles in health and disease.

    abstract::HMGB1/Amphoterin is a ubiquitous, highly conserved DNA-binding protein that can be also released to the extracellular space by various cell types. Extracellular HMGB1 regulates migratory responses of several cell types through binding to RAGE that communicates with the cytoskeleton to regulate cell motility. HMGB1-ind...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/156652407783220750

    authors: Rauvala H,Rouhiainen A

    更新日期:2007-12-01 00:00:00

  • The Effects of Lauric Acid on IPEC-J2 Cell Differentiation, Proliferation, and Death.

    abstract:BACKGROUND:Lauric acid (LA) has antimicrobial effects and the potential to replace antibiotics in feeds to prevent postweaning diarrhea and increase overall swine productivity. The effects of lauric acid on the intestinal epithelial cells remain unclear. METHODS AND RESULTS:This study investigates the effects of LA on...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524020666200128155115

    authors: Yang Y,Huang J,Li J,Yang H,Yin Y

    更新日期:2020-01-01 00:00:00

  • Glycogen and its metabolism.

    abstract::Glycogen is a branched polymer of glucose which serves as a reservoir of glucose units. The two largest deposits in mammals are in the liver and skeletal muscle but many cells are capable synthesizing glycogen. Its accumulation and utilization are under elaborate controls involving primarily covalent phosphorylation a...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524024605761

    authors: Roach PJ

    更新日期:2002-03-01 00:00:00

  • Dopaminergic Genes Polymorphisms and Prefrontal Cortex Efficiency Among Obese People - Whether Gender is a Differentiating Factor?

    abstract:BACKGROUND:Obesity is a chronic condition associated with poorer cognitive functioning. Wisconsin Card Sorting Test (WCST) is a useful tool for evaluating executive functions. In this study, we assessed the association between dopaminergic gene polymorphisms: DAT1 (SLC6A3), COMTVal158Met, DRD4 (48-bp variable number of...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/1566524019666190424143653

    authors: Bieliński M,Lesiewska N,Junik R,Kamińska A,Tretyn A,Borkowska A

    更新日期:2019-01-01 00:00:00

  • Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine.

    abstract::Human induced pluripotent stem cells (hiPSCs) have great potential as a robust source of progenitors for regenerative medicine. The novel technology also enables the derivation of patient-specific cells for applications to personalized medicine, such as for personal drug screening and toxicology. However, the biologic...

    journal_title:Current molecular medicine

    pub_type: 杂志文章,评审

    doi:10.2174/1566524011313050010

    authors: Shtrichman R,Germanguz I,Itskovitz-Eldor J

    更新日期:2013-06-01 00:00:00

  • Beyond the cardiac myofilament: hypertrophic cardiomyopathy- associated mutations in genes that encode calcium-handling proteins.

    abstract::Traditionally regarded as a genetic disease of the cardiac sarcomere, hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease and a significant cause of sudden cardiac death. While the most common etiologies of this phenotypically diverse disease lie in a handful of genes encoding critica...

    journal_title:Current molecular medicine

    pub_type: 杂志文章

    doi:10.2174/156652412800620020

    authors: Landstrom AP,Ackerman MJ

    更新日期:2012-06-01 00:00:00