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L LL-37 Incamake
LL-37, peptide yonyine yica mikorobe mu mubiri wumuntu, ni iyumuryango wa gatolika, igizwe na acide 37 amine, kandi igaragaramo amphipathic α-helical structure. Byibanze bigizwe na neutrophile, birashobora kandi gusohoka na macrophage, monocytes, keratinocytes, nubundi bwoko bwakagari. LL-37 igira uruhare runini mu kurinda ubudahangarwa bw'umuntu, ikagaragaza ibikorwa byinshi by’ibinyabuzima birimo ibikorwa byinshi bya antibacterial antibacterial, immunomodulation, no guteza imbere gukira ibikomere. Irinda neza bagiteri-nziza ya bagiteri, bagiteri-mbi ya bagiteri, fungi, na virusi, byongera ubushobozi bwumubiri bwo kurwanya kwandura) muguhindura chemotaxis yingirabuzimafatizo no gusohora ibintu bitera umuriro, kandi bigatera angiogenezi hamwe no gusana icyarimwe icyarimwe. Hamwe ninyungu nkibikorwa bya antibacterial yagutse, ubushake buke bwo kurwanya ibiyobyabwenge, cytotoxicitike nkeya, hamwe nimirimo ikingira indwara, LL-37 yerekana ubushobozi bukomeye, cyane cyane mukurwanya antibiyotike. Ubushakashatsi kuri LL-37 ntabwo butanga ubumenyi bushya bwo guteza imbere imiti mishya ya antibacterial na immunotherapeutique ahubwo inateza imbere ubushakashatsi bwimbitse mubijyanye na peptide yica mikorobe, butanga ibimenyetso bya siyansi bikomeye byo gukemura ibibazo bijyanye n'indwara zandura, ibikomere bidakira, n'indwara ziterwa na autoimmune.
▎ LL-37 Imiterere
Inkomoko: PubChem |
Urukurikirane: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES Inzira ya molekulari: C 205H 340N 60O.53 Uburemere bwa molekuline: 4493 g / mol Numero ya CAS: 154947-66-7 PubChem CID: 16198951 Synonyme: Cathelicidin ; ropocamptide |
LL -37 Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na LL-37?
LL-37 yavumbuwe bwa mbere nk'icyiciro cy'ibintu bito bito bya peptide muri pupae ya silkworm Samia cynthia ricini n'umuhanga wo muri Suwede witwa Boman HG mu 1980. LL-37 ni peptide ya C-terminal (CAMP, hCAP18) ya cathelicidin antibacterial peptide itera imbaraga za mikorobe, ifata umubiri wa mikorobe ikingira umubiri. (Chen X, 2018). Peptide ya antibacterial igaragara cyane mu nyamaswa, ku bimera, no kuri mikorobe nkeya, kandi ni igice cyingenzi cy’ubudahangarwa bw'umubiri bw’intangangabo. Nka poroteyine y'ibanga, LL-37 igaragara cyane mu ngingo nyinshi no mu ngingo z'umubiri w'umuntu. Ingirabuzimafatizo zitandukanye, zirimo selile epithelale, keratinocytes, selile mast, neutrophile, macrophage, na monocytes, zirashobora kubisohora. Ubwinshi muri ubu bwoko bwa antibiotique burimo 37 - 39 'ibisigisigi bya aside amine ' kandi bifite 0 sisitemu. Bitewe nuburyo bukomeye kuri N-terminal ya peptide ya antibacterial, irashobora gukora 'imiterere ihamye ya amphiphilic '. Antibacterial peptide LL-37 nayo ifite 'amphiphilic α-imiterere '. Kubera imikorere yacyo yo kwica bagiteri zitera indwara, yitwa peptide ya antibacterial. '37 ' mwizina LL-37 birashobora kuba bifitanye isano numubare wibisigisigi bya aside amine. Muri icyo gihe, izwi kandi nka cathelicidin na ropocamptide.
Ni ubuhe buryo bwo gukora LL-37 bwo kurwanya bagiteri zirwanya antibiyotike?
Guhagarika ingirabuzimafatizo ya bagiteri:
LL-37 irashobora kwinjiza muri membrane ya bagiteri, cyane cyane ikagira ingaruka mbi kuri selile irimo fosifatiidylglycerol (DPPG). Bizahungabanya imiterere ya selile ya bagiteri, bityo bigire ingaruka kuri bagiteri . Kurugero, ubushakashatsi bwerekanye ko LL-37 ishobora kwinjiza mumyanya ngirabuzimafatizo ya Gram-positif na Gram-negative bagiteri, bigatuma habaho kwiyongera kwimikorere ya selile, kumeneka kwingirabuzimafatizo, hanyuma amaherezo ya bagiteri.
Igikorwa kinini cya antibacterial ibikorwa:
LL-37 ifite ibikorwa bya antibacterial kurwanya bagiteri zitandukanye zirwanya antibiyotike. Irashobora kurwanya bagiteri nziza ya Gram (nka Staphylococcus aureus, Streptococcus, Enterococcus, nibindi), bacteri za Gram-mbi (nka Pseudomonas aeruginosa, Escherichia coli, Salmonella, nibindi), hamwe nizindi ndwara ziterwa na bagiteri (nka Mycoplasma, Ureaplasma, Mycobactum, nibindi ) . Iki gikorwa cyagutse cya antibacterial ibikorwa bituma LL-37 igira agaciro gakoreshwa mukurwanya ubwoko butandukanye bwa bagiteri irwanya antibiyotike.
Kurimbura biofilm yakozwe:
Biofilm ya bagiteri ni imwe mu mpamvu zingenzi zituma imiti igabanya ubukana bwa bagiteri. Antibacterial peptide LL-37 irashobora gusenya ibinyabuzima byakozwe, bityo bikagabanya imiti ya bagiteri. Kurugero, muri prostate yanduye (PJI) nyuma yo gusimburanya ibihimbano, imiti irwanya bagiteri ziterwa na bagiteri ziterwa na bacteri biofilm ituma ubuvuzi bugorana. Nyamara, LL-37 irashobora kugira uruhare runini rwa antibacterial na bacteriostatic muguhagarika imiterere ya biofilm no gusenya biofilm yakozwe.
Kongera ibikorwa bya antibacterial ya antibiotique:
Ubushakashatsi bwerekanye ko LL-37 igira ingaruka zifatika hamwe na antibiotike zimwe na zimwe. Kurugero, iyo ikoreshejwe hamwe na acide amoxicillin clavulanic aside (AMC), LL-37 irashobora kuzamura cyane ibikorwa bya antibacterial ya AMC.

Inkomoko: Byatangajwe [6]
Ni ubuhe buryo bukoreshwa kuri LL-37?
Guteza imbere kuvugurura amagufwa:
Ubushakashatsi bumwe bwerekanye ko peptide ya antibacterial LL-37 igira ingaruka nziza mu kuvugurura amagufwa. Ubushakashatsi bumwe bwerekanye ko adipose ikomoka kuri adenose ya selile ya mesenchymal stem selile (HADSCs) yari ifite imico itandukanye ya LL-37, kandi byagaragaye ko kwibumbira hamwe kwa LL-37 byagize ingaruka ku bushobozi bwa osteogeneque bwa HADSCs, bugera kuri 4μg / ml. Byongeye kandi, PSeD / hADSCs / LL-37 ikomatanya ryerekanye imiterere ya osteogeneque iruta PSeD / hADSCs, PSeD, hamwe nitsinda ryitsinda ryagaragaye muburyo bwimiterere yimbeba ya Calvarial, byerekana imbaraga nyinshi muburyo bwo kuvugurura amagufwa yubuvuzi.
Ingaruka ya Antibacterial:
Kubuza bagiteri nyinshi zitera indwara:
Ubushakashatsi bumwe bwakoresheje uburyo bwa micro-double dilution kugirango hamenyekane byibuze byibuze bibuza (MIC) ya antibacterial peptide LL-37 kurwanya Escherichia coli, Salmonella, na Staphylococcus aureus. Ibisubizo byerekanye ko LL-37 yagize ingaruka zitandukanye zingaruka zo guhagarika izo bagiteri eshatu zitera indwara, byibuze byibuze byibuze 3.12, 1.56, na 0,78μg / mL. Ikizamini cyo guhagarika ubushyuhe cyerekanaga ko peptide ya antombacterial antombacterial peptide yari igifite ibikorwa byiza mubushyuhe bwinshi. Ibisubizo by'ibizamini bya aside-ishingiro byerekanaga ko LL-37 yagize ibikorwa runaka kuri pH iri hagati ya 2.0 na 12.0, hamwe nibikorwa byiza kuri pH ya 5.0 kugeza 6.0, na -20 ° C nicyo kintu cyiza cyo kubika igihe kirekire [3].
Ingaruka kuri bagiteri irwanya antibiyotike:
Abantu bamwe bakoze ubushakashatsi kuri antibacterial efficacy ya antibacterial peptide LL-37 na nanoparticles ya silver (AgNPs) kurwanya Staphylococcus aureus (S. aureus), mikorobe ikunze kuboneka mu ndwara ziterwa na biofilm. Ibisubizo byerekanye ko LL-37 aribwo buryo bwiza bwa antibacterial agent, hamwe no kugabanya umubare wabakoloni barenga 4 logarithms. Ibinyuranye, ingaruka za nanoparticles ya silver na antibiotique zisanzwe zari mbi, hamwe no kugabanuka kwa koloni munsi ya logarithm 1. Kuvura antibacterial hamwe na rifampicin byongereye cyane kugabanya logarithmic ya AgNPs na gentamicin, ariko yari ikiri hasi cyane ugereranije na LL-37 yakoreshejwe wenyine [4].
Gukoresha mu kwandura ibihaha:
Ubushakashatsi bwerekanye ko Pseudomonas aeruginosa (PA) yabaye ikibazo cyihutirwa cyo kwandura ibihaha no gukomeretsa ibihaha. Peptide ya LL37 ni antibacterial anticacterial anti-PA, ariko kuyikoresha ni bike kubera ko byihuse muri vivo, ibibazo bya biosafeti, hamwe na bioavailable nke. Kubwibyo, kugabanya-kumva-alubumu ishingiye kuri nanodrug sisitemu yo gutanga kugirango itezimbere imikorere ya LL37 irwanya PA muri vivo mugukora imiyoboro ya disulfide intermolecular. Cationic LL37 irashobora gukoreshwa neza binyuze mumikoreshereze ya electrostatike kugirango igire ingaruka nziza ya antibacterial. Peptide ya LL37 yerekanye irekurwa rirambye ryamasaha arenga 48 avuye muri LL37 peptide nanoparticles (LL37 PNP), kandi ingaruka nini ya antibacterial yagaragaye hamwe no kwiyongera kwigihe cyubushakashatsi. Muburyo bwimbeba yanduye PA yanduye, LL37 PNP yagabanije cyane imvugo ya TNF-α na IL-1β kandi igabanya imvune yibihaha. Irerekana ko LL37 PNP ishobora kurushaho kunoza kwandura PA ibihaha hamwe nigisubizo cyakurikiyeho kuruta peptide ya LL37 yubusa [3].
Gukora antibacterial imikorere ya platine:
Ubushakashatsi bwerekanye ko peptide ya antibacterial LL-37 ishobora gukora antibacterial imikorere ya platine yabantu. Nyuma ya platine imaze kuvurwa na LL-37, hejuru yubuso bwakirwa kugirango bamenye mikorobe (Tolls imeze nka Toll) (2) bactericidal / permeability-yongera poroteyine (BPI), azurocidine, peptide ya neutrophil yumuntu (HNP) -1, na myeloperoxidase. Basobanura kandi azurocidine kandi bongera guhuza Escherichia coli, Staphylococcus aureus, na Candida albicans. Byongeye kandi, ndengakamere ya platine ivurwa na LL-37 irashobora kubuza imikurire ya Escherichia coli, cyangwa platine irashobora gukoresha LL-37 kugirango ibuze mikorobe [5].
Gusaba muri sisitemu yo gutanga ibiyobyabwenge
Ubushakashatsi bwerekanye ko peptide ya antibacterial (AMPs) ari icyiciro gishya cya biomolecules gifite imiterere ya antibacterial nini kandi ikaba yarakwegereye abantu kubera kwiyongera kwa antibiyotike yihuse [6] . LL37 niyo yonyine ya cathelicidine ikomoka kuri antibacterial peptide iboneka mu bantu. Hamwe nubushakashatsi bwimbitse, LL37 yerekanye imikorere itandukanye yibinyabuzima, harimo kugenzura igisubizo cyokongoka, chemotaxis yingirabuzimafatizo, guteza imbere gukira ibikomere, na osteogenezi, byashishikarije abantu gukoresha amavuriro atandukanye. Nyamara, ibisobanuro by’amavuriro ya LL37 bigarukira gusa ku kumva ko kwangirika kwa poroteyine, uburozi bushobora kubaho, kutaboneka kwa bioavailable, n'ibindi. Sisitemu zitandukanye zo gutanga, zirimo ibyuma bya nanoparticles, ibikoresho bya polymer, hamwe na sisitemu ishingiye kuri lipide, byatangijwe kugira ngo bigerweho mu kuvura.
Mu gusoza, nka peptide ya bioactive peptide ikora, LL-37 yerekanye ubushobozi bukomeye mubikorwa byubuvuzi. Mu rwego rwo guteza imbere amagufwa mashya, binyuze mu ngaruka ziterwa nuburyo butandukanye nko guteza imbere itandukaniro rya osteoblast nigikorwa, ingaruka za antibacterial, immunomodulation, no guteza imbere angiogenez, yazanye ibyiringiro bishya byo gusana ibikomere. Iyo uhanganye na bagiteri irwanya antibiyotike, mu gusenya mu buryo butaziguye ururenda rw'utugingo ngengabuzima, ikabuza gukora biofilm, no guhuza antibiyotike, biteganijwe ko izaba intwaro ikomeye yo gukemura ikibazo cya bagiteri zidakira imiti. Muri sisitemu yo gutanga ibiyobyabwenge, mugushushanya no kunoza inyandikorugero ya peptide ya antibacterial peptide, kubaka sisitemu nyinshi zo gutanga imiti, no gushakisha ikoreshwa ryibiyobyabwenge, ingaruka zayo zo kuvura zirashobora kurushaho kwiyongera. Muri make, LL-37 ifite ubushobozi mubice byinshi byubuvuzi, harimo guteza imbere amagufwa, ingaruka za antibacterial, gukora imikorere ya antibacterial ya platine, hamwe nibisabwa muri sisitemu yo gutanga ibiyobyabwenge.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Francisco J. Sanchez-Pena ni umushakashatsi muri Universidad Autonoma Benito Juarez de Oaxaca (Kaminuza yigenga ya Benito Juarez ya Oaxaca). Iyi kaminuza yashinzwe mu 1827, ni ikigo cya Leta gikomeye muri Oaxaca, muri Mexico, gitanga gahunda zitandukanye z’amasomo mu bumenyi nka siyansi karemano, ubwubatsi, ubumuntu, n'ubumenyi rusange.
Ubushakashatsi bwa Francisco J. Sanchez-Pena bwibanze kuri Biochemie & Molecular Biology, Microbiology, na Chemistry. Izi disipuline zirimo kwiga uburyo bwimiti ikomoka mubinyabuzima, imiterere ya molekile n'imikorere, imiterere ya mikorobe n'imikoranire yabyo nibidukikije, hamwe nibigize, imiterere, hamwe namategeko yo guhindura ibintu byimiti. Ubushakashatsi muri utwo turere bufite akamaro gakomeye mubuvuzi, ubuhinzi, ubumenyi bwibidukikije, nibindi byinshi. Francisco J. Sanchez-Pena yashyizwe ku rutonde rw'ibivugwa [5].
Imirongo ijyanye
[1] Neville F, Cahuzac M, Konovalov O, n'abandi. Lipid headgroup ivangura na antibicrobial peptide LL-37: Ubushishozi muburyo bwibikorwa [J]. Ikinyamakuru cya Biofiziki, 2006,90 (4): 1275-1287.DOI: 10.1529 / biophysj.105.067595.
[2] Neshani A, Zare H, Eidgahi MRA, n'abandi. LL-37: Gusubiramo umwirondoro wa mikorobe urwanya indwara ziterwa na bagiteri zanduza antibiyotike [J]. Raporo ya Gene, 2019,17: 100519.DOI: 10.1016 / j.genrep.2019.100519.
[3] Li L, Peng Y, Yuan Q, n'abandi. Cathelicidin LL37 iteza imbere itandukaniro rya Osteogenic muri vitro no kuvugurura amagufwa muri vivo [J]. Imipaka muri Bioengineering na Biotechnology, 2021,9.DOI: 10.3389 / fbioe.2021.638494.
[4] Kang J, Dietz MJ, Li B. Antimicrobial peptide LL-37 ni bagiteri yica Staphylococcus aureus biofilms [J]. Ikibanza cya mbere, 2019,14 (6) .DOI: 10.1371 / ikinyamakuru.pone.0216676.
[5] Sanchez-Pena FJ, Romero-Tlalolini MDLA, Torres-Aguilar H, n'abandi. LL-37 Ikurura ibikorwa bya mikorobe muri platine yabantu [J]. Ikinyamakuru mpuzamahanga cya siyansi yubumenyi, 2023,24 (3) .DOI: 10.3390 / ijms24032816.
[6] Lin X, Wang R, Mai S. Iterambere muri sisitemu yo gutanga uburyo bwo kuvura LL37 [J]. Ikinyamakuru cyo gutanga ibiyobyabwenge Ubumenyi n'Ikoranabuhanga, 2020,60.DOI: 10.1016 / j.jddst.2020.102016.
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemewe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.