Hyaluronic acid cues for functional endothelialization of vascular constructs.
Identifieur interne : 000584 ( Ncbi/Merge ); précédent : 000583; suivant : 000585Hyaluronic acid cues for functional endothelialization of vascular constructs.
Auteurs : Samir Ibrahim [États-Unis] ; Anand RamamurthiSource :
- Journal of tissue engineering and regenerative medicine [ 1932-6254 ] ; 2008.
Descripteurs français
- KwdFr :
- Acide hyaluronique (métabolisme), Acide hyaluronique (pharmacologie), Animaux, Cellules cultivées, Coagulation sanguine (), Cytokines (métabolisme), Endothélium vasculaire (), Endothélium vasculaire (cytologie), Endothélium vasculaire (métabolisme), Marqueurs biologiques, Microscopie électronique à balayage, Molécules d'adhérence cellulaire (métabolisme), Néovascularisation physiologique (), Prolifération cellulaire, Protéines et peptides de signalisation intercellulaire (métabolisme), Rats, Techniques de culture cellulaire (), Thrombose (anatomopathologie).
- MESH :
- anatomopathologie : Thrombose.
- cytologie : Endothélium vasculaire.
- métabolisme : Acide hyaluronique, Cytokines, Endothélium vasculaire, Molécules d'adhérence cellulaire, Protéines et peptides de signalisation intercellulaire.
- pharmacologie : Acide hyaluronique.
- Animaux, Cellules cultivées, Coagulation sanguine, Endothélium vasculaire, Marqueurs biologiques, Microscopie électronique à balayage, Néovascularisation physiologique, Prolifération cellulaire, Rats, Techniques de culture cellulaire.
English descriptors
- KwdEn :
- Animals, Biomarkers, Blood Coagulation (drug effects), Cell Adhesion Molecules (metabolism), Cell Culture Techniques (methods), Cell Proliferation, Cells, Cultured, Cytokines (metabolism), Endothelium, Vascular (cytology), Endothelium, Vascular (drug effects), Endothelium, Vascular (metabolism), Hyaluronic Acid (metabolism), Hyaluronic Acid (pharmacology), Intercellular Signaling Peptides and Proteins (metabolism), Microscopy, Electron, Scanning, Neovascularization, Physiologic (drug effects), Rats, Thrombosis (pathology).
- MESH :
- chemical , metabolism : Cell Adhesion Molecules, Cytokines, Hyaluronic Acid, Intercellular Signaling Peptides and Proteins.
- chemical , pharmacology : Hyaluronic Acid.
- chemical : Biomarkers.
- cytology : Endothelium, Vascular.
- drug effects : Blood Coagulation, Endothelium, Vascular, Neovascularization, Physiologic.
- metabolism : Endothelium, Vascular.
- methods : Cell Culture Techniques.
- pathology : Thrombosis.
- Animals, Cell Proliferation, Cells, Cultured, Microscopy, Electron, Scanning, Rats.
Abstract
Current vascular implant materials insufficiently recruit endothelial cells (ECs) to form a normally functional and confluent endothelium, a key challenge to reinstating vascular homeostasis at the surgical site. Recent studies indicate that hyaluronan (HA), a connective tissue GAG whose biological effects are often dictated by its fragment size, may inherently stimulate endothelialization. We previously showed that ECs respond poorly to large HA fragments (10 kDa < MW < 1 MDa), therefore, we currently sought to comprehensively study the effects of exogenous high molecular weight (>1000 kDa) and oligomeric (0.75-10 kDa) ranges on various phenotypic and functional aspects of cultured ECs. HA-1500 (1500 kDa) was enzymatically digested into oligomers under iteratively defined conditions, until a mixture (HA-o) containing a maximal yield of HA-6-mer and 12-mers (33.3 +/- 2.44% and 39.2 +/- 2.68% w/w, respectively) was obtained. The effects of HA-1500, HA-o and pure HA-6-mers on rat aortic ECs were compared. DNA and tube formation assays revealed HA-o and HA-6-mers to stimulate EC proliferation and EC tube formation (angiogenesis) much more than non-HA controls, while HA-1500 had a significant but more modest effect. Both HA-o and HA-6-mers attenuated platelet adhesion and activation on EC layers, while HA-1500 drastically inhibited the same relative to controls. However, flow cytometry and cytokine array studies found that HA-o incited increased expression levels of EC activation markers (ICAM-1, VCAM-1) and promoted the release of select inflammatory cytokines to a greater degree than HA-1500. These results suggest that HA-o and HA-1500 both provide benefits, although frequently of different kinds, to endothelial cell sustenance, proliferation and normal functionality. Thus, tissue engineering scaffolds containing both these cues in optimized ratios could potentially serve as excellent materials for vascular EC regeneration. This forms the basis of our ongoing studies.
DOI: 10.1002/term.61
PubMed: 18265428
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002122
- to stream PubMed, to step Curation: 002122
- to stream PubMed, to step Checkpoint: 001F86
Links to Exploration step
pubmed:18265428Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hyaluronic acid cues for functional endothelialization of vascular constructs.</title><author><name sortKey="Ibrahim, Samir" sort="Ibrahim, Samir" uniqKey="Ibrahim S" first="Samir" last="Ibrahim">Samir Ibrahim</name><affiliation wicri:level="2"><nlm:affiliation>Department of Bioengineering, Clemson University, 501 Rhodes Hall, Clemson, SC 29634, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Bioengineering, Clemson University, 501 Rhodes Hall, Clemson, SC 29634</wicri:regionArea><placeName><region type="state">Caroline du Sud</region></placeName></affiliation></author><author><name sortKey="Ramamurthi, Anand" sort="Ramamurthi, Anand" uniqKey="Ramamurthi A" first="Anand" last="Ramamurthi">Anand Ramamurthi</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2008">2008</date><idno type="RBID">pubmed:18265428</idno><idno type="pmid">18265428</idno><idno type="doi">10.1002/term.61</idno><idno type="wicri:Area/PubMed/Corpus">002122</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002122</idno><idno type="wicri:Area/PubMed/Curation">002122</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002122</idno><idno type="wicri:Area/PubMed/Checkpoint">001F86</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001F86</idno><idno type="wicri:Area/Ncbi/Merge">000584</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Hyaluronic acid cues for functional endothelialization of vascular constructs.</title><author><name sortKey="Ibrahim, Samir" sort="Ibrahim, Samir" uniqKey="Ibrahim S" first="Samir" last="Ibrahim">Samir Ibrahim</name><affiliation wicri:level="2"><nlm:affiliation>Department of Bioengineering, Clemson University, 501 Rhodes Hall, Clemson, SC 29634, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Bioengineering, Clemson University, 501 Rhodes Hall, Clemson, SC 29634</wicri:regionArea><placeName><region type="state">Caroline du Sud</region></placeName></affiliation></author><author><name sortKey="Ramamurthi, Anand" sort="Ramamurthi, Anand" uniqKey="Ramamurthi A" first="Anand" last="Ramamurthi">Anand Ramamurthi</name></author></analytic><series><title level="j">Journal of tissue engineering and regenerative medicine</title><idno type="ISSN">1932-6254</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Biomarkers</term><term>Blood Coagulation (drug effects)</term><term>Cell Adhesion Molecules (metabolism)</term><term>Cell Culture Techniques (methods)</term><term>Cell Proliferation</term><term>Cells, Cultured</term><term>Cytokines (metabolism)</term><term>Endothelium, Vascular (cytology)</term><term>Endothelium, Vascular (drug effects)</term><term>Endothelium, Vascular (metabolism)</term><term>Hyaluronic Acid (metabolism)</term><term>Hyaluronic Acid (pharmacology)</term><term>Intercellular Signaling Peptides and Proteins (metabolism)</term><term>Microscopy, Electron, Scanning</term><term>Neovascularization, Physiologic (drug effects)</term><term>Rats</term><term>Thrombosis (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acide hyaluronique (métabolisme)</term><term>Acide hyaluronique (pharmacologie)</term><term>Animaux</term><term>Cellules cultivées</term><term>Coagulation sanguine ()</term><term>Cytokines (métabolisme)</term><term>Endothélium vasculaire ()</term><term>Endothélium vasculaire (cytologie)</term><term>Endothélium vasculaire (métabolisme)</term><term>Marqueurs biologiques</term><term>Microscopie électronique à balayage</term><term>Molécules d'adhérence cellulaire (métabolisme)</term><term>Néovascularisation physiologique ()</term><term>Prolifération cellulaire</term><term>Protéines et peptides de signalisation intercellulaire (métabolisme)</term><term>Rats</term><term>Techniques de culture cellulaire ()</term><term>Thrombose (anatomopathologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cell Adhesion Molecules</term><term>Cytokines</term><term>Hyaluronic Acid</term><term>Intercellular Signaling Peptides and Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Hyaluronic Acid</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Biomarkers</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Thrombose</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Endothélium vasculaire</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Endothelium, Vascular</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Blood Coagulation</term><term>Endothelium, Vascular</term><term>Neovascularization, Physiologic</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endothelium, Vascular</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Cell Culture Techniques</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Acide hyaluronique</term><term>Cytokines</term><term>Endothélium vasculaire</term><term>Molécules d'adhérence cellulaire</term><term>Protéines et peptides de signalisation intercellulaire</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Thrombosis</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acide hyaluronique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Proliferation</term><term>Cells, Cultured</term><term>Microscopy, Electron, Scanning</term><term>Rats</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Coagulation sanguine</term><term>Endothélium vasculaire</term><term>Marqueurs biologiques</term><term>Microscopie électronique à balayage</term><term>Néovascularisation physiologique</term><term>Prolifération cellulaire</term><term>Rats</term><term>Techniques de culture cellulaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Current vascular implant materials insufficiently recruit endothelial cells (ECs) to form a normally functional and confluent endothelium, a key challenge to reinstating vascular homeostasis at the surgical site. Recent studies indicate that hyaluronan (HA), a connective tissue GAG whose biological effects are often dictated by its fragment size, may inherently stimulate endothelialization. We previously showed that ECs respond poorly to large HA fragments (10 kDa < MW < 1 MDa), therefore, we currently sought to comprehensively study the effects of exogenous high molecular weight (>1000 kDa) and oligomeric (0.75-10 kDa) ranges on various phenotypic and functional aspects of cultured ECs. HA-1500 (1500 kDa) was enzymatically digested into oligomers under iteratively defined conditions, until a mixture (HA-o) containing a maximal yield of HA-6-mer and 12-mers (33.3 +/- 2.44% and 39.2 +/- 2.68% w/w, respectively) was obtained. The effects of HA-1500, HA-o and pure HA-6-mers on rat aortic ECs were compared. DNA and tube formation assays revealed HA-o and HA-6-mers to stimulate EC proliferation and EC tube formation (angiogenesis) much more than non-HA controls, while HA-1500 had a significant but more modest effect. Both HA-o and HA-6-mers attenuated platelet adhesion and activation on EC layers, while HA-1500 drastically inhibited the same relative to controls. However, flow cytometry and cytokine array studies found that HA-o incited increased expression levels of EC activation markers (ICAM-1, VCAM-1) and promoted the release of select inflammatory cytokines to a greater degree than HA-1500. These results suggest that HA-o and HA-1500 both provide benefits, although frequently of different kinds, to endothelial cell sustenance, proliferation and normal functionality. Thus, tissue engineering scaffolds containing both these cues in optimized ratios could potentially serve as excellent materials for vascular EC regeneration. This forms the basis of our ongoing studies.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">18265428</PMID><DateCompleted><Year>2008</Year><Month>10</Month><Day>06</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>01</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1932-6254</ISSN><JournalIssue CitedMedium="Print"><Volume>2</Volume><Issue>1</Issue><PubDate><Year>2008</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Journal of tissue engineering and regenerative medicine</Title><ISOAbbreviation>J Tissue Eng Regen Med</ISOAbbreviation></Journal><ArticleTitle>Hyaluronic acid cues for functional endothelialization of vascular constructs.</ArticleTitle><Pagination><MedlinePgn>22-32</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/term.61</ELocationID><Abstract><AbstractText>Current vascular implant materials insufficiently recruit endothelial cells (ECs) to form a normally functional and confluent endothelium, a key challenge to reinstating vascular homeostasis at the surgical site. Recent studies indicate that hyaluronan (HA), a connective tissue GAG whose biological effects are often dictated by its fragment size, may inherently stimulate endothelialization. We previously showed that ECs respond poorly to large HA fragments (10 kDa < MW < 1 MDa), therefore, we currently sought to comprehensively study the effects of exogenous high molecular weight (>1000 kDa) and oligomeric (0.75-10 kDa) ranges on various phenotypic and functional aspects of cultured ECs. HA-1500 (1500 kDa) was enzymatically digested into oligomers under iteratively defined conditions, until a mixture (HA-o) containing a maximal yield of HA-6-mer and 12-mers (33.3 +/- 2.44% and 39.2 +/- 2.68% w/w, respectively) was obtained. The effects of HA-1500, HA-o and pure HA-6-mers on rat aortic ECs were compared. DNA and tube formation assays revealed HA-o and HA-6-mers to stimulate EC proliferation and EC tube formation (angiogenesis) much more than non-HA controls, while HA-1500 had a significant but more modest effect. Both HA-o and HA-6-mers attenuated platelet adhesion and activation on EC layers, while HA-1500 drastically inhibited the same relative to controls. However, flow cytometry and cytokine array studies found that HA-o incited increased expression levels of EC activation markers (ICAM-1, VCAM-1) and promoted the release of select inflammatory cytokines to a greater degree than HA-1500. These results suggest that HA-o and HA-1500 both provide benefits, although frequently of different kinds, to endothelial cell sustenance, proliferation and normal functionality. Thus, tissue engineering scaffolds containing both these cues in optimized ratios could potentially serve as excellent materials for vascular EC regeneration. This forms the basis of our ongoing studies.</AbstractText><CopyrightInformation>Copyright (c) 2008 John Wiley & Sons, Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ibrahim</LastName><ForeName>Samir</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Bioengineering, Clemson University, 501 Rhodes Hall, Clemson, SC 29634, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ramamurthi</LastName><ForeName>Anand</ForeName><Initials>A</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>C06RR018823</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>EB006078-01A1</GrantID><Acronym>EB</Acronym><Agency>NIBIB NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P20RR016461</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Tissue Eng Regen Med</MedlineTA><NlmUniqueID>101308490</NlmUniqueID><ISSNLinking>1932-6254</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015415">Biomarkers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015815">Cell Adhesion Molecules</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016207">Cytokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D036341">Intercellular Signaling Peptides and Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>9004-61-9</RegistryNumber><NameOfSubstance UI="D006820">Hyaluronic Acid</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015415" MajorTopicYN="N">Biomarkers</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001777" MajorTopicYN="N">Blood Coagulation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015815" MajorTopicYN="N">Cell Adhesion Molecules</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018929" MajorTopicYN="N">Cell Culture Techniques</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004730" MajorTopicYN="N">Endothelium, Vascular</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006820" MajorTopicYN="N">Hyaluronic Acid</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D036341" MajorTopicYN="N">Intercellular Signaling Peptides and Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008855" MajorTopicYN="N">Microscopy, Electron, Scanning</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018919" MajorTopicYN="N">Neovascularization, Physiologic</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013927" MajorTopicYN="N">Thrombosis</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2008</Year><Month>2</Month><Day>12</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2008</Year><Month>10</Month><Day>7</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2008</Year><Month>2</Month><Day>12</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">18265428</ArticleId><ArticleId IdType="doi">10.1002/term.61</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Sud</li></region></list><tree><noCountry><name sortKey="Ramamurthi, Anand" sort="Ramamurthi, Anand" uniqKey="Ramamurthi A" first="Anand" last="Ramamurthi">Anand Ramamurthi</name></noCountry><country name="États-Unis"><region name="Caroline du Sud"><name sortKey="Ibrahim, Samir" sort="Ibrahim, Samir" uniqKey="Ibrahim S" first="Samir" last="Ibrahim">Samir Ibrahim</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000584 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000584 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= pubmed:18265428
|texte= Hyaluronic acid cues for functional endothelialization of vascular constructs.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:18265428" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |