LL-375 mg tab

▎ LL-37 Qauv

Source: PubChem

Sequence: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES Molecular Formula: C 205H 340N 60O53 Molecular Luj: 4493 g / mol CAS Nr .: 154947-66-7 PubChem CID: 16198951 Synonyms: Catholicidin; ropocamptide

▎ LL-37 Kev Tshawb Fawb

Kev tshawb fawb keeb kwm ntawm LL-37 yog dab tsi?

LL-37 tau pom thawj zaug raws li cov chav kawm ntawm cationic me peptide tshuaj nyob rau hauv lub pupae ntawm silkworm Samia cynthia ricini los ntawm Swedish kws tshawb fawb Boman HG nyob rau hauv 1980. LL-37 yog C-terminal peptide (CAMP, hCAP18) ntawm tib neeg cathelicidin tshuaj tua kab mob thiab cov kab mob tseem ceeb hauv peptide. physiological functions nyob rau hauv chemotaxis, txhawb lub qhov txhab kaw, thiab angiogenesis (Chen X, 2018). Antibacterial peptides muaj dav nyob rau hauv cov tsiaj, nroj tsuag, thiab ib tug me me ntawm microorganisms, thiab lawv yog ib feem tseem ceeb ntawm innate kev tiv thaiv ntawm vertebrates. Raws li cov protein secretory, LL-37 yog dav nyob rau hauv ntau lub cev thiab cov ntaub so ntswg ntawm tib neeg lub cev. Ntau lub hlwb, suav nrog cov hlwb epithelial, keratinocytes, mast hlwb, neutrophils, macrophages, thiab monocytes, tuaj yeem zais nws. Feem ntau ntawm cov tshuaj tua kab mob no muaj 37 - 39 'amino acid residues' thiab muaj 0 cysteine ​​​​. Vim yog lub hauv paus muaj zog ntawm N-terminal txoj hauj lwm ntawm cov tshuaj tua kab mob peptide, nws tuaj yeem tsim qhov ruaj khov 'amphiphilic helical qauv'. Cov tshuaj tua kab mob peptide LL-37 kuj tseem muaj 'amphiphilic α-helical qauv'. Vim nws txoj haujlwm ntawm kev tua cov kab mob pathogenic, nws muaj npe hu ua antibacterial peptide. Lub '37' nyob rau hauv lub npe LL-37 tej zaum yuav muaj feem xyuam rau tus naj npawb ntawm nws cov amino acid residues. Tib lub sijhawm, nws tseem hu ua cathelicidin thiab ropocamptide.

Yuav ua li cas yog lub mechanism ntawm kev txiav txim ntawm LL-37 tiv thaiv kab mob-resistant kab mob?

Disrupting cov kab mob cell membrane: 

LL-37 tuaj yeem ntxig rau hauv cov kab mob ntawm tes, tshwj xeeb tshaj yog muaj kev puas tsuaj rau cov cell membrane uas muaj phosphatidylglycerol (DPPG). Nws yuav cuam tshuam cov qauv ntawm cov kab mob cell membrane, yog li exerting ib tug bactericidal nyhuv ^[1] . Piv txwv li, cov kev tshawb fawb tau pom tias LL-37 tuaj yeem nkag mus rau hauv cov cell membranes ntawm cov kab mob Gram-positive thiab Gram-negative, uas ua rau muaj kev nce hauv permeability ntawm cov cell membrane, xau ntawm cov ntsiab lus ntawm tes, thiab thaum kawg tuag ntawm cov kab mob.

Broad-spectrum antibacterial kev ua haujlwm: 

LL-37 muaj cov tshuaj tua kab mob tiv thaiv ntau yam kab mob uas tiv thaiv kab mob. Nws tuaj yeem tiv thaiv kab mob Gram-positive (xws li Staphylococcus aureus, Streptococcus, Enterococcus, thiab lwm yam), kab mob Gram-negative (xws li Pseudomonas aeruginosa, Escherichia coli, Salmonella, thiab lwm yam), thiab lwm yam kab mob (xws li Mycoplasma, Ureaplasma, thiab lwm yam ^. ) Qhov dav-spectrum antibacterial kev ua ub no ua rau LL-37 muaj peev xwm siv tau tus nqi hauv kev sib ntaus sib tua ntawm ntau hom tshuaj tua kab mob.

Ua kom puas cov tsim biofilm: 

Bacterial biofilm yog ib qho ntawm cov laj thawj tseem ceeb rau cov tshuaj tiv thaiv kab mob pathogenic. Cov tshuaj tua kab mob peptide LL-37 tuaj yeem rhuav tshem cov txheej txheem biofilm, yog li txo cov tshuaj tiv thaiv kab mob. Piv txwv li, nyob rau hauv cov kab mob sib koom ua ke (PJI) tom qab kev sib koom tes sib koom ua ke, cov tshuaj tiv thaiv ntawm cov kab mob pathogenic tshwm sim los ntawm cov kab mob biofilm ua rau kev kho mob nyuaj. Txawm li cas los xij, LL-37 tuaj yeem ua lub luag haujlwm tiv thaiv kab mob thiab bacteriostatic los ntawm inhibiting qhov tsim ntawm biofilm thiab rhuav tshem cov tsim biofilm.

Txhim khu kev ua haujlwm ntawm cov kab mob tua kab mob ntawm cov tshuaj tua kab mob: 

Cov kev tshawb fawb tau pom tias LL-37 muaj kev sib koom ua ke nrog qee yam tshuaj tua kab mob. Piv txwv li, thaum siv nrog amoxicillin clavulanic acid (AMC), LL-37 tuaj yeem txhim kho cov kab mob tua kab mob ntawm AMC.

Source: PubMed ^[6]

Cov ntawv thov rau LL-37 yog dab tsi?

Txhawb cov pob txha regeneration: 

Qee cov kev tshawb fawb tau pom tias cov tshuaj tua kab mob peptide LL-37 muaj txiaj ntsig zoo rau kev tsim cov pob txha. Qee qhov kev tshawb fawb tau pom tias tib neeg adipose-derived mesenchymal qia hlwb (hADSCs) tau coj los ua ke nrog ntau qhov sib txawv ntawm LL-37, thiab nws tau pom tias qhov concentration ntawm LL-37 muaj kev cuam tshuam rau lub peev xwm osteogenic ntawm hADSCs, ncav cuag lub ncov ntawm 4μg / ml. Tsis tas li ntawd, PSeD / hADSCs / LL-37 ua ke scaffold tau pom ntau dua osteogenic zog dua li PseD / hADSCs, PseD, thiab tswj pawg scaffolds hauv cov nas calvarial defect qauv, qhia tias muaj peev xwm loj hauv kev kho cov pob txha.

Antibacterial nyhuv:

Inhibition ntawm ntau yam kab mob pathogenic: 

Qee qhov kev tshawb fawb tau siv cov txheej txheem micro-double dilution los txiav txim qhov tsawg kawg nkaus inhibitory concentration (MIC) ntawm cov tshuaj tua kab mob peptide LL-37 tiv thaiv Escherichia coli, Salmonella, thiab Staphylococcus aureus. Cov txiaj ntsig tau pom tias LL-37 muaj qhov sib txawv ntawm cov teebmeem inhibitory ntawm peb cov kab mob pathogenic, nrog rau qhov tsawg kawg nkaus inhibitory concentrations yog 3.12, 1.56, thiab 0.78μg / mL, feem. Qhov kev ntsuam xyuas thermal stability tau pom tias cov tshuaj tua kab mob recombinant peptide tseem muaj kev ua haujlwm zoo ntawm qhov kub thiab txias. Cov txiaj ntsig ntawm acid-base stability test tau pom tias LL-37 muaj qee yam kev ua haujlwm ntawm pH ntau ntawm 2.0 txog 12.0, nrog rau kev ua haujlwm zoo tshaj plaws ntawm pH ntawm 5.0 txog 6.0, thiab -20 ° C yog qhov zoo tshaj plaws rau kev khaws cia ntev ^[3].

Cov txiaj ntsig ntawm cov kab mob tua kab mob-resistant: 

Qee tus neeg tau kawm txog kev siv tshuaj tua kab mob ntawm cov tshuaj tua kab mob peptide LL-37 thiab nyiaj nanoparticles (AgNPs) tiv thaiv Staphylococcus aureus (S. aureus), kab mob uas feem ntau pom nyob rau hauv cov kab mob biofilm. Cov txiaj ntsig tau pom tias LL-37 yog cov tshuaj tua kab mob zoo tshaj plaws, nrog rau kev txo qis hauv colony suav ntau dua 4 logarithms. Nyob rau hauv sib piv, cov teebmeem ntawm cov nyiaj nanoparticles thiab cov pa tshuaj tua kab mob yog cov neeg pluag, nrog ib tug txo nyob rau hauv colony suav tsawg dua 1 logarithm. Kev kho cov kab mob sib xyaw ua ke nrog rifampicin ua rau muaj kev txo qis logarithmic ntawm AgNPs thiab gentamicin, tab sis nws tseem qis dua li ntawm LL-37 siv ib leeg ^[4].

Kev siv rau kev mob ntsws pulmonary: 

Cov kev tshawb fawb tau pom tias Pseudomonas aeruginosa (PA) tau dhau los ua qhov nyuaj rau kev mob ntsws ntsws thiab mob ntsws. LL37 peptide yog cov tshuaj tua kab mob zoo tiv thaiv kab mob PA, tab sis nws daim ntawv thov raug txwv vim nws tshem tawm sai hauv vivo, teeb meem biosafety, thiab bioavailability tsawg. Yog li ntawd, kev txo qis-rhiab albumin-raws li nanodrug tus me nyuam system tau tsim los txhim kho kev ua tau zoo ntawm LL37 tiv thaiv PA hauv vivo los ntawm kev tsim cov ntawv cog lus intermolecular disulfide. Cationic LL37 tuaj yeem ua tau zoo los ntawm kev sib cuam tshuam electrostatic kom ua kom cov kab mob zoo dua qub. Lub LL37 peptide tau pom tias muaj kev tso tawm ntau dua 48 teev los ntawm LL37 peptide nanoparticles (LL37 PNP), thiab txuas ntxiv cov kab mob tua kab mob tau sau tseg nrog qhov nce hauv lub sijhawm incubation. Hauv tus qauv nas ntawm tus kab mob PA mob ntsws, LL37 PNP txo qhov kev qhia ntawm TNF-α thiab IL-1β thiab txo qis kev raug mob ntsws. Nws qhia tau hais tias LL37 PNP tuaj yeem txhim kho PA pulmonary kab mob zoo dua thiab cov lus teb tom qab inflammatory dua li LL37 peptide dawb ^[3].

Activating antibacterial kev ua haujlwm ntawm platelets: 

Cov kev tshawb fawb tau taw qhia tias cov tshuaj tua kab mob peptide LL-37 tuaj yeem ua kom cov kab mob ua haujlwm ntawm tib neeg platelets. Tom qab platelets raug kho nrog LL-37, qhov kev qhia saum npoo ntawm receptors rau kev paub txog cov kab mob (Tshooj-zoo li receptors (TLRs) 2 thiab -4, CD32, CD206, Dectin-1, CD35, LOX-1, CD41, CD62P, thiab αIIbβ3 integrin muaj feem xyuam rau cov tshuaj tiv thaiv kab mob tam sim no) thiab cov tshuaj tiv thaiv kab mob 80CDs (tam sim no) CD86, thiab HLA-ABC) tau nce, thiab cov kab mob tua kab mob tau tso tawm: bactericidal / permeability-increasing protein (BPI), azurocidin, human neutrophil peptide (HNP)-1, thiab myeloperoxidase. Lawv kuj txhais azurocidin thiab txhim khu kev khi rau Escherichia coli, Staphylococcus aureus, thiab Candida albicans. Tsis tas li ntawd, lub supernatant ntawm platelets kho nrog LL-37 tuaj yeem cuam tshuam kev loj hlob ntawm Escherichia coli, lossis platelets tuaj yeem siv lawv cov LL-37 los tiv thaiv kev loj hlob ntawm microbial ^[5].

Kev siv hauv kev xa tshuaj

Cov kev tshawb fawb tau hais tias cov tshuaj tua kab mob peptides (AMPs) yog ib chav kawm tshiab ntawm biomolecules nrog dav-spectrum antibacterial thaj chaw thiab tau nyiam cov xim vim qhov nce sai ntawm cov tshuaj tiv thaiv kab mob ^[6] . LL37 yog tib lub cathelicidin-derived antibacterial peptide pom nyob rau hauv tib neeg. Nrog rau kev tshawb fawb tob, LL37 tau qhia ntau yam kev ua haujlwm lom neeg, suav nrog kev tswj cov kab mob inflammatory, chemotaxis ntawm lub cev tiv thaiv kab mob, txhawb kev kho qhov txhab, thiab osteogenesis, uas tau txhawb ntau yam kev siv tshuaj kho mob. Txawm li cas los xij, kev txhais lus kho mob ntawm LL37 yog txwv los ntawm nws qhov rhiab heev rau protease degradation, muaj peev xwm toxicity, tsis zoo bioavailability, thiab lwm yam. Ntau lub tshuab xa, nrog rau cov hlau nanoparticles, cov ntaub ntawv polymer, thiab cov txheej txheem lipid-based, tau raug qhia kom ua tiav cov kev siv kho mob.

Nyob rau hauv xaus, raws li ib tug multifunctional bioactive peptide, LL-37 tau pom zoo muaj peev xwm nyob rau hauv kev kho mob daim ntawv thov. Hais txog kev txhawb nqa pob txha, los ntawm kev sib koom ua ke ntawm ntau lub tswv yim xws li txhawb kev sib txawv ntawm osteoblast thiab kev ua ub no, cov tshuaj tiv thaiv kab mob, immunomodulation, thiab txhawb nqa angiogenesis, nws tau coj kev cia siab tshiab rau kev kho pob txha. Thaum cuam tshuam nrog cov kab mob tshuaj tua kab mob, los ntawm kev rhuav tshem cov cell membrane ncaj qha, inhibiting kev tsim ntawm biofilms, thiab kev sib koom ua ke nrog cov tshuaj tua kab mob, nws xav tias yuav dhau los ua riam phom muaj zog los daws cov teeb meem ntawm cov kab mob tshuaj tiv thaiv. Hauv kev xa tshuaj, los ntawm kev tsim thiab ua kom zoo rau cov kab mob peptide templates, tsim ntau lub tshuab xa tshuaj, thiab tshawb xyuas cov kev siv tshuaj sib xyaw ua ke, nws cov txiaj ntsig kev kho mob tuaj yeem txhim kho ntxiv. Nyob rau hauv luv luv, LL-37 muaj peev xwm nyob rau hauv ntau yam ntawm kev kho mob daim ntawv thov, nrog rau kev txhawb cov pob txha regeneration, antibacterial teebmeem, activating antibacterial muaj nuj nqi ntawm platelets, thiab kev siv nyob rau hauv cov tshuaj xa systems.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Francisco J. Sanchez-Pena yog tus kws tshawb fawb ntawm Universidad Autonoma Benito Juarez de Oaxaca (Autonomous Benito Juarez University of Oaxaca). Tsim los ntawm 1827, lub tsev kawm ntawv no yog lub tsev kawm ntawv tseem ceeb hauv Oaxaca, Mexico, muab ntau yam kev kawm hauv kev kawm xws li natural sciences, engineering, humanities, thiab social sciences.

Francisco J. Sanchez-Pena txoj kev tshawb fawb tsom mus rau Biochemistry & Molecular Biology, Microbiology, thiab Chemistry. Cov kev qhuab qhia no suav nrog kev kawm txog cov txheej txheem tshuaj lom neeg hauv cov kab mob, cov qauv molecular thiab kev ua haujlwm, cov yam ntxwv ntawm microbial thiab lawv cov kev cuam tshuam nrog ib puag ncig, nrog rau cov muaj pes tsawg leeg, cov khoom, thiab kev hloov pauv ntawm cov tshuaj lom neeg. Kev tshawb fawb hauv cov cheeb tsam no muaj kev siv tseem ceeb hauv tshuaj, kev ua liaj ua teb, kev tshawb fawb ib puag ncig, thiab lwm yam. Francisco J. Sanchez-Pena tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [5].

▎ Cov Lus Qhia Tseem Ceeb

[1] Neville F, Cahuzac M, Konovalov O, et al. Lipid headgroup kev ntxub ntxaug los ntawm antimicrobial peptide LL-37: Kev nkag siab rau hauv kev ua haujlwm [J]. Biophysical Journal, 2006,90(4):1275-1287.DOI:10.1529/biophysj.105.067595.

[2] Neshani A, Zare H, Eidgahi MRA, et al. LL-37: Kev tshuaj xyuas ntawm cov tshuaj tua kab mob tiv thaiv kab mob rhiab thiab tshuaj tua kab mob-tiv taus tib neeg cov kab mob [J]. Gene Reports, 2019,17:100519.DOI:10.1016/j.genrep.2019.100519.

[3] Li L, Peng Y, Yuan Q, et al. Catelicidin LL37 Txhawb nqa Osteogenic sib txawv hauv vitro thiab pob txha rov tsim dua tshiab hauv vivo [J]. Frontiers hauv Bioengineering thiab Biotechnology, 2021,9.DOI:10.3389/fbioe.2021.638494.

[4] Kang J, Dietz MJ, Li B. Antimicrobial peptide LL-37 yog bactericidal tiv thaiv Staphylococcus aureus biofilms[J]. Plos Ib, 2019,14(6).DOI:10.1371/journal.pone.0216676.

[5] Sanchez-Pena FJ, Romero-Tlalolini MDLA, Torres-Aguilar H, et al. LL-37 Ua rau Cov Tshuaj Tiv Thaiv Kab Mob Hauv Tib Neeg Platelets [J]. International Journal of Molecular Sciences, 2023,24(3).DOI:10.3390/ijms24032816.

[6] Lin X, Wang R, Mai S. Advances in delivery systems for therapeutic application of LL37[J]. Phau ntawv Journal of Drug Delivery Science thiab Technology, 2020,60.DOI:10.1016/j.jddst.2020.102016.

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.