KPV 30mg we yu de yuz

▎ TKPV Struktrɔ

Sos:PubChem., ɛn di ɔda wan dɛn

IUPAC Kɔndens:H-Lys-Pro-Val-OH Mɔlikul Fɔmula: C 16H 30N 4O4 Molikul Weyt: 342.43g/mol CAS Nɔmba: 67727-97-3 PubChem CID: 125672. Di wan dɛn we de wok Sinonim dɛn: Msh (11-13);alfa-Msh (11-13);AKT-(11-13)

▎ KPV Risach

Wetin na di risach bakgrɔn fɔ KPV?

KPV na tripεptida we kכmכt frכm α-melanosayt-stimulεt כmon (α-MSH). α-MSH na polipεptida כmon wit mכltipכl bayolojikal fכnshכn dεm, we de ple imכtant rol fכ rεgεl di skin pigmεnt, imyun rεgulεshכn, εn כda aspek dεm. as pat pan α-MSH, dεn bin aylכt KPV εn dεn bin stכdi am dip wan. Pan ɔl we sɔm prɔgrɛs dɔn de pan di mɛdikal fild insay di las ia, di tritmɛnt opshɔn fɔ inflammatory bowel disease (IBD) stil nɔ satisfay, ɛn di ɔpreshɔn rit stil ay. So, fɔ fɛn nyu ɛn fayn tritmɛnt dɛn dɔn bi wok we pɔsin fɔ du kwik kwik wan. IBD inklud ɔlsa kɔlayt, Kron sik, ɛn ɔda tin dɛn, we kin sho se dɛn gɛt krɛse intestinal inflamɛns ɛn dɛn kin rili afɛkt di kwaliti fɔ layf fɔ di sik pipul dɛn. Di tritmɛnt we dɛn de yuz naw na fɔ tek drɔgs ɛn ɔpreshɔn, bɔt dɛn ɔl tu gɛt sɔm tin dɛn we dɛn nɔ ebul fɔ du. insay di las ia dεm, dεn dεskrεb di anti-inflammatory ifekt dεm fכ melanocortin pεpti dεm lεk α-MSH insay dεkstran sכlfet sכdiכm (DSS) kolεtis insay mays. dis de gi wan klyu fכ stכdi di anti-inflammatory pכtεnshal fכ KPV. α-MSH gεt fכnshכn dεm lεk imyun rεguleshכn εn inflameshn εliviεshכn, εn dεn kin kכnsidr di tripεptida KPV we kכmכt frכm am bak fכ posisibul fכ gεt di sem anti-inflammatory prכpati dεm.

Wetin na di mɛkanism fɔ akshɔn fɔ KPV?

Mekanism fכ akshכn na כlsεraytiv kolεt

Impruv stebiliti ɛn rεktal administreshɔn kɔvinant: 

KPV (Lys-Pro-Val) na tripεptida we kכmכt frכm α-MSH (α-melanocyte-stimulating hormone) εn i gεt anti-inflammatory ifekt εgεst kolεt. כltu, di KPV sכlushכn de rili כnstebul we dεn de gi am rεktal, we de afekt in tεrapi ifekt. In di stכdi, sistεamin-grafted γ-polyglutamic acid (SH-PGA) bin sεntez bay we dεn kכmbayn sistiamin wit di kכbכksiyl grup fכ γ-PGA. Witout yuz kros-linking ejen, wan 4% polimכr kכntεnt SH-PGA haydrojεl bin fכm tru di sεlf-krכs-linkin כf sכlfhaydril grup dεm. di KPV/SH-PGA haydrojel sho wan elastik mכdulus (G') we hכy pas di kכrεspכndεnt viskos mכdulus (G'') na 0.01-10 Hz, we sho gud mεkanikal stεbiliti εn shia tinin bihayv, we bεnεfit fכ rεktal administreshכn. At di sem tεm, di stεbiliti כf KPV in di SH-PGA haydrojεl bin sכmtεm εnhans. כnli 30% pan KPV bin kכmכt frכm di KPV/SH-PGA haydrojεl insay 20 minit, we dεn fכlכ kכntinyu fכ rilis bihayv ^[1]..

Fɔ mek di sik dɛn we de sho se pɔsin gɛt kɔlaytis nɔ bɔku: 

Tru εkspεriεns pan rat wit כlsεraytiv kolεt we 2,4,6-trinitrobenzene sulfonic acid (TNBS) indyuz, di εnhans tεrapi ifekt כf di KPV/SH-PGA haydrojεl pan kolεt bin kכnfכm. Afta rεktal administreshכn כf di KPV/SH-PGA haydrojεl, kolεtis simptom dεm inklud weit lכs εn sik aktiviti indeks skכ dεm bin sכmtεm εlivεt. apat frכm dat, tritmεnt wit di KPV/SH-PGA haydrojεl bin mek di kכlon sכt insay rat dεm we dεn injεkt wit TNBS εn i ridyus di lεvεl fכ di kכlon mayloperoxidase. afta tritmεnt wit di KPV/SH-PGA haydrojεl, di mכfכlכji fכ di kכlon, inklud di εpitεlial barεri, kript, εn intakt gכblεt sεl dεm, bin rεstכr. di sem tεm, di KPV/SH-PGA haydrojεl rεdכks di εksprεshכn fכ pro-inflammatory saytokεn dεm lεk tכmכro nεkrכsis fכktכ α εn intalyukin 6 ^[1]..

Mekanism fכ akshכn in maws mכdel dεm fכ inflammatory bowel disease

DSS kolaytis mכdel: Insay di DSS kolaytis mכdel, tritmεnt wit KPV bin mek i rεkכvεshכn bifo εn i bin rili εnhans di wet rεkכvεshכn. histכlכjik wan, di inflammatory infiltrashכn in KPV-trit mכs dεm bin sכmtεm rεdכks, we dεn kכnfכm bay di siknifikant dεkrεshכn in di aktvכti fכ myeloperoxidase (MPO) insay di kכlon tisu afta KPV tritmεnt ^[2]..

CD45RB (hi) transfכm kolεtis mכdel: 

fכ sכpכt di tin dεm we wi bin dכn fכnshכn, KPV tritmεnt fכ transfכr kolεtis bin lid to di sik rεkכvεshכn, weit rεkכvεshכn, εn rεdכkshכn pan inflammatory chenj dεm frכm histכlכjik pεspεktiv ^[2]..

MC1Re/e maus model: 

insay mays dεm we de εksprεs wan nכn-fכnshכnal melanocortin-1 rεsεptכr (MC1Re/e), KPV tritmεnt sev כl di animal dεm na di tritmεnt grup frכm day di tεm we DSS kolεt de. dis sho se di anti-inflammatory ifekt fכ KPV lεk se i atכs pat pan di indipεndεnt frכm MC1R signal ^[2]..

mεkanism fכ akshכn in brכnkial εpitεlial sεl inflameshn

I nhibit NF-κB signalin: 

insay imכtalayz hכman brכnkial εpitεlial sεl dεm, di melanocortin-rεlatεd pεptida KPV εn di agonist α-MSH fכ di aywe εpitεlium (MC3R) inhεbit NF-κB signal bay we dεn inhεbit di nyuklia import fכ p65RelA εn aktibכt εpitεlial MC3R, rispεktivli. sכm spεshal, di ifekt we KPV gεt de riliyt to in nyuklia imכpכt, we kin inhεbit di nyuklia translכkeshכn fכ p65RelA we dεn lεbul wit YFP. di sem tεm, di binding sayt dεm fכ KPV εn Imp-α/β de pan p65RelA, we i kin involv fכ blכk importin-α armadillo domεn 7 εn 8 ^{[3] .}.

Mεkanism fכ akshכn in kεmothεrapi-indyus כral mכkusayz

Antibacterial, anti-inflammatory, ɛn ripa ifɛkt dɛn: 

Yuz tεmprachכ-sεnsitiv PLGA-PEG-PLGA (PPP) as di matris εn epigallocatechin-3-gallate (EGCG) wit inhεrent antibakterial aktiviti as di adheshon εnhansa, wan in-situ mכkus adhesive haydrojεl (PPP_E) bin saksesfulli pripia. Di tripεptida KPV bin sכlv insay di kol PPP_2% E prεkursכr sכlushכn as mכdel drog fכ pripia di KPV@PPP_2% E haydrojεl. di anti-inflammatory aktiviti εn di pכtεnshal fכ protεkt sεl maygrεshכn fכ KPV insay di PPP-2% E haydrojεl bin mεnten fayn fayn wan. Apat frɔm dat, di KPV@PPP_2% E bin gɛt strɔng antibacterial ifɛkt agens Staphylococcus aureus. we dεn aplay di KPV@PPP_2% E haydrojεl to di gingival mכkus fכ rat dεm wit kεmothεrapi-indyus כral mכkusayz, i kin transfכm kwik kwik wan to haydrojεl εn adhe to di wund sεf fכ 7 awa, we de bכku bכku wan impruv di it intake εn wet rεkכvεshכn fכ di rat dεm. di sem tεm, bay we i de promuot di εksprεshכn fכ CK10 εn PCNA, di KPV@PPP_E haydrojεl dεn tu rεpair di tisu mכfכlכji fכ di כlsεrayt gingiva bak fayn fayn wan. apat frכm dat, di KPV@PPP_2% E haydrojεl sכmtεm inhεbit inflammatory saytokεn dεm inklud IL-1β εn TNF-α, εn ​​di sem tεm i upregulate IL-10 ^[4]..

Sos:PubMed ^{[5] we dɛn pul am.}

Wetin na di klinik aplikeshɔn kes dɛm fɔ KPV drɔgs?

Tritmɛnt fɔ ɔlsɛrativ kɔlayt

Administreshכn tru sεlf-krכslinkin haydrojεl: 

insay wan stכdi, dεn sεntez di sistiamin-grafted γ-polyglutamic acid (SH-PGA) εn mek am to haydrojεl fכ stεbyul di tripεptida KPV ^[1] . di KPV/SH-PGA haydrojel sho gud tεrapi ifekt in wan rat mכdel fכ כlsεraytiv kolεt we 2,4,6-trinitrobenzene sulfonic acid (TNBS) indyuz. sכm spεshal, afta dεn gi di rεktal administreshכn, di kolכtis sכmtεm dεm lεk di wet lכs εn di sik aktiviti indeks skכ dεm bin sכmtεm εliviet, εn i kin bak fכ mek di kכlon sכt insay rat dεm we dεn injεkt wit TNBS εn ridyus di lεvεl fכ di kכlon mayloperoxidase. di sem tεm, di mכfכlכji fכ di kכlon, inklud di εpitεlial barεri, kript, εn intakt gכblεt sεl dεm, bin rεstכr afta tritmεnt wit di KPV/SH-PGA haydrojεl, εn di haydrojεl dεn rεdכks di εksprεshכn fכ pro-inflammatory saytokεn dεm lεk tכmכro nεkrכsis fכktכ α εn intalyukin 6 bak.

Administreshɔn tru dual-nɛtwɔk haydrojɛl: 

כda stכdi kכnstrכkt wan dual-netwכk haydrojεl (PMSP) we fכm bay maleated γ-polyglutamic acid εn thiolated γ-polyglutamic acid tru thiol-maleimide kכros-link εn sεlf-oksidashכn fכ tiol dεm ^[5] . dis haydrojel kin spεshal adhere to di inflamed mכkus pas di hεlty mכkus, εn i gεt gud mεkanikal trεnk εn bayolojikal adheshon. KPV, as mכdel dכg, i izi fכ kapchכ PMSP tru ilektrostatik intarakshכn, so dat i de mεnten in bayolojikal aktiviti fכ lכng tεm כnda ay tεmprachכ kכndishכn dεm. In rat wit kolεt we TNBS indyuz, afta rεktal administreshכn כf PMSP-KPV, di alleviating ifekt כf KPV pan kolεtis bin sכmtεm improv, εn di εpitεlial barεri fכ di kכlon bin ifektivli rεstכr. apat frכm dat, PMSP-KPV de rεgεl di intestinal fכla bak εn i sכmtεm inkrεs di bכku bεnεfit maykro כganism dεm na di intestinal.

Fɔ kemotɛrapi-indyuz ɔral mucositis

wan in-situ mכkus adhesive haydrojel (PPP_E) bin pripia yuz tεmprachכ-sεnsitiv PLGA-PEG-PLGA (PPP) as di matris εn epigallocatechin-3-gallate (EGCG) as di adheshon εnhansa ^[4] . Di tripεptida KPV bin sכlv insay di kol PPP_2% E prεkursכr sכlushכn as mכdel drog fכ pripia di KPV@PPP_2% E haydrojεl. Dis haydrojel gɛt anti-inflammatory, antibacterial, ɛn ripa ifɛkt pan kemotɛrapi-indyuz ɔral mucositis. spεshal wan, i kin mεnten di anti-inflammatory aktiviti fכ KPV εn di pכtεnshal fכ protεkt sεl maygrεshכn, εn i gεt strכng antibakterial ifekt εgεst Staphylococcus aureus. afta dεn administreshכn to di gingival mכkus fכ rat dεm wit kεmothεrapi-indyus כral mכkus, di PPP_2% E prεkursכr sכlushכn transfכm kwik kwik wan to haydrojεl εn adεr to di wund sεf fכ 7 awa. Tritmεnt wit di KPV@PPP_2% E haydrojεl bכku impruv di it intayk εn wet rεkכvεshכn fכ di rat dεm, protεkt di εksprεshכn fכ CK10 εn PCNA, wel ripa di tisu mכfכlכji fכ di כlsεrayt gingiva, εn di sem tεm sכmtεm inhεbit inflammatory cytokines lεk IL-1β εn TNF-α, εn ​​upregulated di εksprεshכn fכ IL-10. dis haydrojel gεt antibakterial ifekt bak pan di gingival כlsa wund dεm we infεkt wit mεtisilin-rεsistant Staphylococcus aureus (MRSA), εn i de sכmtεm inhεbit di infiltεshכn fכ inflammatory sεl dεm insay di sכbmכkus tisu.

Tritmɛnt fɔ inflammatory bowel disease

Sɔm stɔdi dɔn sho se KPV kin bi nyu tritmɛnt fɔ inflammatory bowel disease (IBD) ^[6] . insay hכman intestinal εpitεlial sεl dεm (Caco2-BBE εn HT29-Cl.19A) εn hכman T sεl dεm (Jurkat), afta dεn stimulate wit pro-inflammatory cytokines, di ad we dεn ad KPV kin inhεbit di aktibכshכn fכ NF-κB εn MAP kinase inflammatory signaling pathways εn ridyus di sekreshכn fכ pro-inflammatory cytokines. di stכdi fכnshכn se KPV de akt tru hPepT1 we dεn εksprεs insay imyun εn intestinal εpitεlial sεl dεm. apat frכm dat, insay maws mכdel dεm fכ kolεt we dεkstran sכlfet sכdiכm (DSS) εn TNBS indyuz, כral administreshכn fכ KPV kin ridyus di εksprεshכn fכ pro-inflammatory cytokines εn di insidεns fכ kolεtis.

Fכ kכnklud, as bayoaktiv sכbstans wit big pכtεnshal, KPV de sho yunik advantej dεm fכ trit difrεn sik dεm. insay di fild fכ inflammatory bowel disease, weda insay maws mכdel εkspεriεns כ insay di εksplכreshכn fכ difrεn administreshכn mεtכd dεm fכ כlsεraytiv kolεt, KPV kin ifektivli ridyus inflammatory infiltration, impruv tisu mכfכlכji, rεgεl saytokεn εksprεshכn, εn εksyεrt sכm anti-inflammatory ifekt dεm tru mεkanism dεm lεk PepT1 transpכt. insay di tritmεnt fכ di kεmothεrapi-indyus כral mכkusaytis, di haydrojεl we gεt KPV we dεn pripia wit spεsifi k matris εn adheshon εnhansa nכ kin כnli mεnten in anti-inflammatory εn sεl maygrεshכn-prכmot aktiviti dεm bכt i gεt pawaful antibakterial abiliti, we de impruv di rilayt simptom dεm fכ rat bכku bכku wan εn protεkt di tisu ripa. Pan ɔl we di klinik aplikeshɔn kes dɛm we de naw fɔ KPV stil smɔl, di risach rizɔlt dɛm we de naw de sho ful wan in tritmɛnt valyu. Insay di fyuchu, if dɛn kin ebul fɔ mek tin dɛn we go mek dɛn ebul fɔ du dip risach fɔ mek di mɛrɛsin stebul ɛn di we aw dɛn de gi dɛn, fɔ mek di klinik indikɛshɔn dɛn go bifo, ɛn fɔ mek di klinik monitarin ɛn manejmɛnt strɔng, dɛn de op se KPV go briŋ mɔ ay kwaliti ɛn efishɔnal tritmɛnt opshɔn fɔ mɔ pasɛnt dɛn ɛn ple mɔ impɔtant pat pan klinik tritmɛnt.

Bɔt di pɔsin we rayt di buk

Di tin dɛn we wi dɔn tɔk bɔt ɔp, na ɔl di tin dɛn we Cocer Peptides dɔn du risach, ɛdit ɛn kɔmpilayt.

Sayɛns Jɔnal Author

Dalmasso G na risachman pan di fild fɔ mɛrɛsin, wit risach dairekshɔn dɛm we de kɔba mɛrɛsin, bayɔkemistri, ɛn jenɛtiks, ɛn ɔda eria dɛm. I dɔn wok na bɔku big big institiushɔn dɛn, lɛk Yunivasiti Klɛmɔnt Ɔvɛn (UCA), CHU Klɛmɔnt Fɛrand, INRAE, Instityut Nashɔnal de la Sante ɛn de la Richɛsh Mɛdikal (Inserm), Klɛmɔnt Yunivasiti, Jɔjia Stet Yunivasiti, Ɛmɔri Yunivasiti, Yunivasiti Kɔt di Azur, ɛn Yunivasiti Nashɔnal Rio Kuarto. Dɛn institiushɔn ya gɛt bɔku nem pan dɛn yon fild, ɛn di wok we Dalmasso G dɔn du wit dɛn dɔn ɛp fɔ mek di disiplin dɛn we gɛt fɔ du wit dɛn go bifo. Di tin dɛm we i dɔn fɛn pan risach kin rili impɔtant to di divɛlɔpmɛnt fɔ mɛdikal sayɛns, mɔ fɔ mek di tritmɛnt autkam fɔ di sik ɛn di kwaliti fɔ layf we di sikman dɛn gɛt bɛtɛ. Dalmasso G de list insay di rεfrεns fכ saytεshכn [6].

▎ Saytayshɔn dɛn we gɛt fɔ du wit dis

[1] Sun J, Xue P, Liu J, ɛn ɔda pipul dɛn. Self-Kros-Linked Hydrogel of Cysteamine-Grafted γ-Polyglutamic Acid Stabilized Tripeptide KPV fɔ Aliviet TNBS-Induse Ɔlsɛrativ Kɔlayt insay Rat[J]. Acs Bayomaterials Sayns & Ɛnjinia, 2021,7(10):4859-4869.DOI:10.1021/acsbiomaterials.1c00792.

[2] Konnengiesser K, Maaser C, Haydemann J, ɛn ɔda pipul dɛn. Melanocortin-derived tripeptide KPV gεt anti-inflammatory pכtεnshal in murin mכdel dεm fכ inflammatory bowel disease[J]. Inflammatory Bowel Disiz, 2008,14(3):324-331.DOI:10.1002/ibd.20334.

[3] Land S C. Inhibishכn fכ sεlyul εn sistεmik inflameshn kכy dεm na hכman brכnkial εpitεlial sεl dεm bay melanocortin-rεlatεd pεptida dεm: mεkanism fכ KPV akshכn εn wan rol fכ MC3R agonist dεm.[J]. Int ɛ rnash ɔ nal J ɔ rnal ɔ f Fisiɔlɔji, Patɔfysiɔlɔji ɛn Famakɔlɔji, 2012,4(2):59-73. https://pubmed.ncbi.nlm.nih.gov/22837805/ Di wan dɛn we de stɔdi bɔt di Baybul.

[4] Shao W, Chen R, Lin G, ɛn ɔda pipul dɛn. in situ mucoadhesive haydrojel we de kapchכ tripεptida KPV: di anti-inflammatory, antibacterial εn ripair ifekt pan kεmothεrapi-indyus כral mכkosaytis[J]. Bayomaterials Sayns, 2021,10(1):227-242.DOI:10.1039/d1bm01466h.

[5] Zhao Y, Xue P, Lin G, ɛn ɔda pipul dɛn. wan KPV-binding dכbl-nεtwכk haydrojεl de rεstכr di gכt mכkus barεri insay wan inflamed kכlon[J]. Akta Bayomaterialia, 2022,143:233-252.DOI:10.1016/j.actbio.2022.02.039.

[6] Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, ɛn ɔda pipul dɛn. PepT1-mεdiet tripεptida KPV כptek de ridyus intestinal inflameshn[J]. Gastroenteroloji, 2008,134(1):166-178.DOI:10.1053/j.gastro.2007.10.026.

ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN 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.