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▎ LL-37 Ɔvaviu
LL-37, di wan ol antimaykrobial pεptida insay di mכtalman bכdi, de insay di katolik famili, i kכnsis fכ 37 amino asid dεm, εn i gεt amfipatik α-hεlikal strכkchכ. di nyutrofil dεm fכ mek am, i kin kכmכt bak bay makrofag dεm, monosayt dεm, kεratinosayt dεm, εn כda kayn sεl dεm. LL-37 de ple imכtant rol insay hכman imyun difεns, i de sho mכltipכl bayolojikal fכnshכn dεm we inklud brכd-spεktrum antibakterial aktiviti, imyunmodyulεshכn, εn prכmoshכn fכ wund hεl. i de inhεbit gram-positiv baktri dεm, gram-nεgεtiv baktri dεm, fכnshכn, εn vayrus dεm fayn fayn wan, i de εnhans di bכdi in anti-infεkshכn kapasiti)bay we i de rεgεl di kεmotaksis fכ di imyun sεl dεm εn sekreshכn fכ inflammatory fכktכ dεm, εn i de mek di angiojεnεsis εn tisu ripa wan tεm. wit advantej dεm lεk brכd-spεktrum antibakterial aktiviti, lכw prכpεnsi fכ drog rεsistεns, lכw saytכtoksisiti, εn imyunomodulatory fכnshכn, LL-37 de sho sכbstanshכl pכtεnshal, patikyular fכ adrεs antibaytik rεsistεns. Risach pan LL-37 nɔ jɔs de gi nyu insayt fɔ divɛlɔp nyu antibacterial ɛn immunotherapeutic ejen bɔt i de promot dip ɛksplɔrɔshɔn insay di fild fɔ antimaikrobial peptide, we de gi impɔtant sayɛns pruf fɔ sɔlv prɔblɛm dɛn we gɛt fɔ du wit infɛkshɔn sik dɛn, wund dɛn we nɔ de dɔn, ɛn ɔtoimyun dizayd.
▎ LL-37 Struktrɔ
Sos: PubChem |
Sikyɔn: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES Mɔlikul Fɔmula: C 205H 340N 60O53 Molikul Weyt: 4493 g/mol CAS Nɔmba: 154947-66-7 PubChem CID: 16198951. Di wan dɛn we de wok Di tin dɛn we gɛt di sem minin: Cathelicidin;ropocamptide |
▎ LL-37 Risach
Wetin na di risach bakgrɔn fɔ LL-37?
LL-37 bin fכs fכs fכ no as wan klas כf kεtyכnik sכm pεptida sכbstans dεm na di pupa dεm fכ di silkwom Samia cynthia ricini bay di Swedish sayɛnsman Boman HG insay 1980. LL-37 na di C-tεrminal pεptida (CAMP, hCAP18) fכ hכman katelisidin antibakterial pεptida, we kin inkrεs di rεsistεns to maykrobial invashכn εn de ple imכtant fysiolojikal fכnshכn dεm na kεmotaksis, we de protεkt wund kכloshכn, εn angiojεnεsis (Chen X, 2018). di antibakterial pεpti dεm de bכku bכku wan insay animal, plant, εn sכm sכm maykro כganism dεm, εn dεn na imכtant pat pan di innate imyuniti fכ vεrbret dεm. as sekretri protin, LL-37 de bכku bכku wan insay mכtalman כgan dεm εn tisu dεm na di mכtalman bכdi. difrεn sεl dεm, lεk di εpitεlial sεl dεm, kεratinosayt dεm, mast sεl dεm, nyutrofil dεm, makrofag dεm, εn monosayt dεm kin kכl am. כl dis kayn antibaytik gεt 37 - 39 'amino asid rεsidεns' εn i gεt 0 sistayn. biכs fכ di strכng bεsisiti na di N-tεrminal posishכn fכ di antibakterial pεptida, i kin fכm wan stebul 'amphifilik hεlikal strכkchכ'. di antibakterial pεptida LL-37 gεt bak wan 'amphifilik α-hεlikal strכkchכ'. biכs di wok we i de du fכ kil baktri dεm we de mek sik, dεn gi am di nem antibakterial pεptida. di '37' we de insay di nem LL-37 kin riliyt to di nכmba fכ in amino asid rεsidεns dεm. na di sem tεm, dεn kin kכl am bak katelisidin εn ropokamptayd.
Wetin na di mεkanism fכ akshכn fכ LL-37 εgεst antibaytik-rεsistant baktri dεm?
disrupt di baktriyal sεl mεmbran:
LL-37 kin insay di baktriyal sεl mεmbran, spεshal wan we i gεt distrכktiv ifekt pan di sεl mεmbran we gεt fכsfatidylglisεrol (DPPG). i go disrupt di strכkchכ fכ di baktriyal sεl mεmbran, so dat i go mek baktri kil ifekt [1] . fכ egzampl, stכdi dεm dכn fכnshכn se LL-37 kin insay di sεl mεmbran dεm fכ כl tu di Gram-positiv εn Gram-nεgεtiv baktri dεm, we de mek di sεl mεmbran inkrεs pan di pεrmiabiliti fכ di sεl mεmbran, di lik we di sεl mεmbran de lik, εn te di baktri dεm de day.
Brod-spεktrum antibakterial aktiviti:
LL-37 gεt antibakterial aktiviti εgεst difrεn baktri dεm we de rεsist antibaytik. i kin akt agens Gram-positiv baktri dεm (lεk Staphylococcus aureus, Streptococcus, Enterococcus, εn כda wan dεm), Gram-negativ baktri dεm (lεk Pseudomonas aeruginosa, Escherichia coli, Salmonella, εn כda wan dεm), εn כda baktri dεm we de mek sik (lεk Mycoplasma, Ureaplasma, Mycobacterium, εn כda wan dεm) [2] . dis brayt-spεktrum antibakterial aktiviti de mek LL-37 gεt pכtεnshal aplikεshכn valyu fכ kכmbat difrεn tכp dεm fכ antibaytik-rεsistant baktri dεm.
Fɔ pwɛl di bayɔfilm we dɔn fɔm:
baktriyal bayofilm na wan pan di imכtant rizin dεm fכ di drog rεsistεns fכ di baktri dεm we de mek sik. di antibakterial pεptida LL-37 kin pwεl di bayofilm we fכm, so dat de ridyus di drog rεsistεns fכ baktri dεm. fכ egzampl, insay di prosthεtik jכint infεkshכn (PJI) afta dεn riples di artifishal jכint, di drog rεsistεns fכ di pathogenic baktri dεm we di baktriyal bayofilm kכz de mek di tritmεnt at. כltu, LL-37 kin ple wan ifektiv antibakterial εn bakteriostatik rol bay we i de inhεbit di fכmeshכn fכ di bayofilm εn destroy di fכm bayofilm.
Fɔ mek di antibacterial aktiviti fɔ di antibacterial aktiviti bɛtɛ:
Stɔdi dɔn sho se LL-37 gɛt sinajɛstik ifɛkt wit sɔm antibaytik dɛn. fכ egzampl, we dεn yuz am wit amoxicillin clavulanic acid (AMC), LL-37 kin strכng wan εnhans di antibacterial aktiviti fכ AMC.

Sos:PubMed [6] we dɛn pul am.
Wetin na di aplikeshɔn dɛn fɔ LL-37?
Fɔ mek di bon dɛn gɛt nyu layf:
sכm stכdi dεn sho se di antibakterial pεptida LL-37 gεt fayn ifekt pan bon rigεnεreshכn. sכm risεch dεn sho se dεn kכlt hכman adipos-dεriv mεsenchymal stεm sεl dεm (hADSCs) wit difrεn kכnsantreshכn fכ LL-37, εn dεn fכnshכn se di kכnsantreshכn fכ LL-37 bin gεt impak pan di כsteogenic abiliti fכ hADSC dεm, we rich wan pik na 4μg/ml. Apat fr dat, di PSeD/hADSCs/LL-37 kכmbaynshכn sכf sho mכr supεriכr כstiojεnik prכpati dεm pas di PSeD/hADSCs, PSeD, εn kכntrol grup sכfכld dεm na di rat kalvarial dεfεkt mכdel, we sho se i gεt hכy pכtεnshal in klinik bon rigεnεreshכn.
Antibakterial ifɛkt: .
Inhibishכn fכ mכltipכl pathogenic baktri dεm:
sכm risεch yuz di maykro-dכbl dilushכn mεtכd fכ no di minimכm inhibitory kכnsantreshכn (MIC) fכ di antibakterial pεptida LL-37 εgens Escherichia coli, Salmonella, εn Staphylococcus aureus. di risalts sho se LL-37 bin gεt difrεn digri fכ inhibitory ifekt pan dεn tri pathogenic baktri dεm, wit di minim inhibitory kכnsantreshכn we na 3.12, 1.56, εn 0.78μg/mL, rispεktivli. di tεmכl stεbiliti tεst sho se di rεkombinεnt antibakterial pεptida stil gεt gud aktvכti na ay tεmprachכ. di asid-bεys stεbiliti tεst risכlt sho se LL-37 gεt sכm aktvכti na pH rεnj 2.0 to 12.0, wit di bεst aktiviti na pH 5.0 to 6.0, εn -20°C na di bεst kכndishכn fכ lכng tεm stכrej [3]..
Ifekt pan baktri dɛm we nɔ de tek antibayɔtik:
Sɔm pipul dɛn bin stɔdi di antibacterial efficacy fɔ di antibacterial peptide LL-37 ɛn silva nanoparticles (AgNPs) agens Staphylococcus aureus (S. aureus), we na wan maykroɔganism we dɛn kin si pan infɛkshɔn dɛn we gɛt fɔ du wit bayɔfilm. di rizulεt sho se LL-37 na di mכst ifektiv antibakterial ejen, wit rεdukshכn pan kכloni kכnt we pas 4 lכgaritm. difrεnt frכm dat, di ifekt dεm we silva nanopartikl dεm εn kכvεshכnal antibaytik dεm bin po, wit rεdukshכn pan di kכloni kכnt we less dan 1 lכgaritm. di antibakterial kכmbaynshכn tritmεnt wit rifampicin sכmtεm inkrεs di lכgaritmik rεdukshכn fכ AgNPs εn jεntamisin, bכt i bin stil sכmtεm lכw pas di wan fכ LL-37 we dεn yuz nכmכ [4]..
Aplikeshɔn insay pulmonari infɛkshɔn:
Stɔdi dɔn sho se Pseudomonas aeruginosa (PA) dɔn bi wan kwik chalenj fɔ pulmonari infɛkshɔn ɛn fɔ injuri na di lɔng. di LL37 pεptida na ifektiv antibakterial ejen εgεst PA strayn dεm, bכt in aplikεshכn de limited biכs fכ in rεpid kliarεns in vivo, bayosεfty ishu dεm, εn lכw bayoavaylabl. כl dis mek dεn dכn divεlכp wan ridyus-sεnsitiv albumin-bεys nanodrug dεlivεri sistεm fכ impruv di pεrformεns fכ LL37 εgεst PA in vivo bay we dεn de fכm intamכlikul disulfayd bכnd dεm. kεshכnik LL37 kin ifektivli εnkapsulεt tru εlektrostatik intarakshכn fכ εksyεrt wan impruv antibakterial ifekt. di LL37 pεptida sho wan sustayn rilis fכ mכr dan 48 awa frכm di LL37 pεptida nanopartikl dεm (LL37 PNP), εn wan εkstend antibakterial ifekt bin notis wit di inkrεs pan di inkכbeshכn tεm. In wan maws mכdel fכ akyu PA pulmonari infεkshכn, LL37 PNP sכmtεm rεdכks di εksprεshכn fכ TNF-α εn IL-1β εn εliviet lכng injuri. i sho se LL37 PNP kin impruv PA pulmonari infεkshכn εn di inflammatory rεspכns we de afta dat pas di fri LL37 pεptida [3] ..
fכ aktiv di antibakterial fכnshכn fכ di pletlεt dεm:
stכdi dεn dכn sho se di antibakterial pεptida LL-37 kin aktibכt di antibakterial fכnshכn fכ di mכtalman pletlet dεm. afta dεn trit di pletlet dεm wit LL-37, di sכfayz εksprεshכn fכ di rεsεpכta dεm fכ rεkכgnεz maykro כganism dεm (Toll-like rεsεpכta dεm (TLR) 2 εn -4, CD32, CD206, Dectin-1, CD35, LOX-1, CD41, CD62P, εn αIIbβ3 integrin) εn mכlikul dεm we riliyt to prεzεnt antijen to T limfosayt dεm (CD80, CD86, εn HLA-ABC) de inkrεs, εn antibakterial mכlikul dεm de kכmכt: baktrisaydal/pεrmiabiliti-inkrεsiv protin (BPI), azurocidin, hכman nyutrofil pεptida (HNP)-1, εn mayloperoxidase. Dɛn kin translet azurocidin bak ɛn mek di binding to Escherichia coli, Staphylococcus aureus, ɛn Candida albicans bɛtɛ. pan tap dat, di supεrnatant fכ di pletlet dεm we dεn trit wit LL-37 kin inhibit di growth fכ Escherichia coli, כ di pletlet dεm kin yuz dεn LL-37 fכ inhibit di maykrobial growth [5]..
Aplikeshɔn insay drɔg delivri sistɛm dɛn
stכdi dεn dכn mεnshכn se antibakterial pεptida dεm (AMP) na nyu klas fכ bayomכlikul dεm wit brayt spεktrum antibakterial prכpati dεm εn dεn dכn atrak atεnshכn biכs fכ di rεpid inkrεs pan antibaytik rεsistεns [6] . LL37 na di wan ol antibakterial pεptida we kכmכt frכm kathelicidin we dεn fכnshכn insay mכtalman. wit dip risach, LL37 dכn sho difrεn bayolojikal fכnshכn dεm, we inklud fכ rεgεl di inflammatory rεspכns, kεmotaksis fכ di imyun sεl dεm, fכ protεkt wund hεl, εn כstiojεnεsis, we dεn inkכrej difrεn klinik aplikεshכn dεm. כltu, di klinik transleshכn fכ LL37 na limited bay in sεnsitiviti to proteas dεgradashכn, pכtεnshal tכksisiti, pwεl bayoavaylabl, εtk.Dεn introdכks difrεn dεlivεri sistεm dεm, inklud mεtal nanopartikl dεm, polimכr mεtirial dεm, εn lipid-bεys sistεm dεm, fכ achy tεrapi aplikεshכn dεm.
fכ kכnklud, as mכltifכnshכnal bayoaktiv pεptida, LL-37 dכn sho big pכtεnshal in klinik aplikεshכn dεm. pan tεm fכ protεkt bon rigεnεreshכn, tru di sinagεstik ifekt dεm fכ mכltipכl mεkanism dεm lεk fכ protεkt כsteoblast difrεns εn aktiviti, antibakterial ifekt, imyunomodyulεshכn, εn fכ promuot angiojεnεsis, i dכn bכn nyu op fכ bon injuri ripa. We dɛn de dil wit baktri dɛm we nɔ de tek antibayɔtik, bay we dɛn de pwɛl di sɛl mɛmbran dairekt wan, we de mek di bayɔfilm dɛn nɔ mek, ɛn we dɛn de wok togɛda wit antibayɔtik, dɛn tink se i go bi pawaful wɛpɔn fɔ sɔlv di prɔblɛm we baktri dɛm we nɔ de tek drɔgs gɛt. insay dכg dεlivεri sistεm, bay we dεn disayn εn optimiz antibakterial pεptida tεmplat dεm, kכnstrכkt mכltipכl dכg dεlivεri sistεm dεm, εn εksplכr di kכmbayn aplikεshכn fכ dכg dεm, in klinik tritmεnt ifekt kin εnhans mכr. in shot, LL-37 gεt pכtεnshal in mכltipכl aspek dεm fכ klinik aplikεshכn dεm, inklud fכ protεkt bon rigεnεreshכn, antibakterial ifekt dεm, aktibכt di antibakterial fכnshכn fכ pletlet dεm, εn aplikεshכn insay dכg dεlivεri sistεm dεm.
Bɔt di pɔsin we rayt di buk
Di tin dɛm we wi dɔn tɔk bɔt ɔp na ɔl di risach, ɛdit ɛn kɔmpilayt na Cocer Peptides.
Sayɛns Jɔnal Author
Fransisko J. Sanchez-Pena na wan risachman na Yunivasiti Ɔtonoma Bɛnito Juarez de Oaxaca (Ɔtonɔm Bɛnito Juarez Yunivasiti ɔf Oaxaca). Dis yunivasiti we dɛn bin mek insay 1827, na wan impɔtant pɔblik institiushɔn na Oaxaca, Mɛksiko, we de gi bɔku bɔku akademik program dɛn pan tin dɛn lɛk natura sayɛns, injinɛri, umaniti, ɛn soshal sayɛns.
Francisco J. Sanchez-Pena in risach de fos pan Bayokemistri & Mɔlikul Bayoloji, Maykrobayoloji, ɛn Kwɛstyɔn. dis disiplin dεm involv fכ stכdi di kεmikכl prכsεs dεm insay כganism dεm, mכlikul strכkchכ dεm εn fכnshכn dεm, maykrobial kכntribyushכn dεm εn dεn intarakshכn wit di envayroment, εn bak di kכmכshכn, prכpati dεm, εn transfכmeshכn rul dεm fכ kεmikכl sכbstans dεm. Risach pan dɛn tin ya gɛt bɔku tin dɛn fɔ du pan mɛrɛsin, agrikalchɔral biznɛs, sayɛns bɔt envayrɔmɛnt, ɛn ɔda tin dɛn. Francisco J. Sanchez-Pena de na di list insay di rɛfrɛns fɔ saytayshɔn [5].
▎ Saytayshɔn dɛn we gɛt fɔ du wit dis
[1] Nɛvil F, Kahuzak M, Kɔnɔvalov O, ɛn ɔda pipul dɛn. Lipid hεdgrup diskriminεshכn bay antimaykrobial pεptida LL-37: Insayt in mεkanism fכ akshכn[J]. Bayofizikal J ɔ rnal, 2006,90(4):1275-1287.DOI:10.1529/bayofisj.105.067595.
[2] Neshani A, Zare H, Eidgahi MRA, ɛn ɔda pipul dɛn. LL-37: Rivyu fכ antimaykrobial profayl εgεst sεnsitiv εn antibaytik-rεsistant hכman baktriyal patכgens[J]. Jin Ripɔt, 2019,17:100519.DOI:10.1016/j.jɛnrɛp.2019.100519.
[3] Li L, P eng Y, Yuan Q, ɛn ɔda pipul dɛn. Cathelicidin LL37 de Promot Osteogenic Difrεns in vitro εn Bon Rijεnεreshכn in vivo[J]. Frontiers in Bayoɛnjɛnɛri ɛn Bayoteknɔlɔji, 2021,9.DOI:10.3389/fbioe.2021.638494.
[4] Kang J, Dietz MJ, Li B. Antimaykrobial pεptida LL-37 na baktrisaydal εgεst Stafylokɔk ɔrεs bayofεm[J]. Plos Wan, 2019,14(6).DOI:10.1371/jɔnal.pon.0216676.
[5] Sanchεz-Pεna F. J., Rכmεro-Tlalolini MDLA, Tכrεs-Aguilar H, εt al. LL-37 de Trigεr Antimaykrobial Aktvכti insay hכman Plεtlεt dεm[J]. Int ɛ rnash ɔ nal J ɔ rnal ɔ f Mɔlikul Sayns, 2023,24(3).DOI:10.3390/ijms24032816.
[6] Lin X, Wang R, Mai S. Advans in dilivεri sistεm fכ di tεrapi aplikεshכn fכ LL37[J]. J ɔ rnal ov Drug Delivri Sayns ɛn Tɛknɔlɔji, 2020,60.DOI:10.1016/j.jddst.2020.102016.
ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL DI INFƆMƐSHƆN DISƐMƐNƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.