Lub Koom Haum Ntawm Kev Laus Microenvironment Thiab Tumor Progression

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"Kev laus" feem ntau txhais tau tias yog lub sij hawm-dependent functional poob cuam tshuam rau kab mob, thiab lub sij hawm-dependent tsub zuj zuj ntawm cellular puas nyob rau hauv cov kab mob yog suav hais tias yog ib tug general ua rau kev laus. Ntawm qhov tod tes, qog nqaij hlav thiab senescence tshwm sim los ntawm cov txheej txheem sib txawv: cov qog yog tshwm sim los ntawm kev ua kom lub cev tsis muaj zog, thaum lub cev tsis muaj zog yog qhov tsis muaj zog. Cov txiaj ntsig kev loj hlob txawv txav tuaj yeem ua rau qog nqaij hlav. Los ntawm qhov kev xav no, "mob" thiab "senescence" yog ob qho kev sib txawv ntawm cov txheej txheem ntawm cov cellular puas. Molecular kos npe rau ntawm cuaj hlwb ntawm tib neeg kev laus: genomic instability, poob ntawm proteostasis, telomere attrition, mitochondrial tsis ua hauj lwm, hloov epigenetic yam ntxwv, hloov intercellular kev sib txuas lus, dysregulated nutrient sensing, cellular senescence, thiab stem cell.

Anti-aging thiab anti-tumor:sib

Kev laus microenvironment thiab qog kev loj hlob:Kev laus microenvironment drives qog hlav. Kev sib cuam tshuam ntawm cov qog hlwb thiab cov senescent microenvironment, raws li pom los ntawm qhov tseeb tias senescence reprograms interstitial fibroblast pejxeem, extracellular matrix (ECM), thiab kev tiv thaiv kab mob kom tsav cov qog pib thiab kev loj hlob. Kev laus microenvironment kuj tuaj yeem cuam tshuam tsis zoo rau kev tswj cov qog cell teb rau kev kho tshuaj antitumor. Ntau yam cuam tshuam nrog kev hloov pauv ntawm cov ntaub so ntswg senescent ua rau qhov kev hloov pauv ntawm tus kheej rov ua dua tshiab rau hauv kev loj hlob thiab kev loj hlob, lossis kev loj hlob raug ntes (xws li, cellular senescence), apoptosis, thiab degradation ntawm lwm cov cellular thiab cov ntaub so ntswg structural Cheebtsam. Qhov kev nce ntxiv hauv cov qog nqaij hlav thiab ntau yam ntawm cov yam ntxwv degenerative hauv cov ntaub so ntswg thiab cov hlwb nrog lub hnub nyoog yog muaj feem xyuam nrog kev sib cuam tshuam ntawm cov kab mob hauv zos thiab cov kab mob microenvironments ntawm kev laus thiab lawv txoj kev koom tes rau cov qog pib thiab kev loj hlob. Thaum lub sij hawm kev laus, cov ntaub so ntswg sib txawv thoob plaws hauv lub cev tuaj yeem cuam tshuam qhov sib txawv reprogramming, cuam tshuam cov qog loj hlob thiab kev loj hlob.

Matrix homeostasis hauv kev laus:Lub matrix microenvironment nyob rau hauv cov ntaub so ntswg, muaj ntau yam Cheebtsam, xws li fibroblasts, endothelial hlwb, pericytes, adipocytes, ECM, thiab lub cev tiv thaiv kab mob, plays lub luag hauj lwm tseem ceeb nyob rau hauv cov ntaub so ntswg homeostasis. Fibroblasts yog cov feem ntau stromal feem ntawm cov ntaub so ntswg thoob plaws hauv lub cev. Cov kev hloov pauv uas tshwm sim hauv fibroblasts thaum lub sijhawm laus kuj tuaj yeem sib txawv ntawm qhov chaw ntawm lub cev thiab feem ntau koom nrog kev laus. Antagonistic pleiotropy nyob rau hauv cov ntsiab lus ntawm kev laus yog txhais raws li ib tug tib yam genetic traits uas induces ib tug zoo thiab noj qab haus huv-hloov phenotype thaum ntxov nyob rau hauv lub neej, tab sis nyob rau hauv cov laus cov kab mob nws yuav ua teeb meem. Cellular senescence yog ib qho piv txwv classic ntawm antagonistic pleiotropy, thiab tsub zuj zuj ntawm senescent hlwb yog ib qho ntawm cov yam ntxwv tseem ceeb ntawm kev laus. Ib qho ntawm cov yam ntxwv tseem ceeb ntawm cellular senescence yog qhov kev hloov pauv ntawm cov noob caj noob ces, nrog rau cov hlwb ua kom muaj kev tso tawm ntawm proinflammatory cytokines, chemokines, kev loj hlob yam, thiab proteases; Qhov no secretome yog txhais raws li ib tug secretory phenotype txuam nrog senescence. SASP tau xav tias muaj kwv yees li 75 yam tsis pub lwm tus paub, ntau yam uas tau txheeb xyuas hauv kev tshawb fawb siv cov qauv ntawm cov kab mob oncogene-induced senescence, thiab tej zaum yuav muaj txiaj ntsig zoo, ceeb toom rau lub cev tiv thaiv kab mob rau cov ntaub so ntswg puas los yog xav tau kom tshem tawm cov hlwb senescent, tab sis kuj tseem yuav muaj txiaj ntsig zoo. teeb meem vim nws lub luag haujlwm hauv kev tsav cov qog cell ntxeem tau thiab kev loj hlob. Nws cov cellular senescence plays lub luag haujlwm tseem ceeb hauv kev tswj cov qog hlwb, qhov twg cov kev hloov pauv ntawm oncogenic ntawm cov hlwb ib txwm tuaj yeem ua rau lawv cov senescence, pib tiv thaiv lawv txoj kev loj hlob. Txawm hais tias homeostatic tseem ceeb ntawm cov txheej txheem senescence hauv stromal hlwb, cov hnub nyoog cuam tshuam txog kev sib sau ntawm SASP cov hlwb nyob rau lub sijhawm tuaj yeem rov ua dua cov thawj thiab metastatic microenvironments rau hauv lub xeev uas muaj txiaj ntsig zoo rau kev loj hlob ntawm tes, yog li txhawb kev mob qog noj ntshav. Hom kev pib ntawm cellular senescence induced los ntawm oncogenes, replication, kev nyuaj siab, los yog kev kho mob ho hloov lub SASP yam secreted los ntawm cov hlwb, thiab tsis yog tag nrho cov cellular senescence yog tsim sib npaug, los yog nws yeej tsis tau qhia tias senescence.

Cistanche deserticola hmoov ntxivzoo txhim khophysiology thiab anti-tumor thiab anti-aging

Qauv thiab kev laus ECM:Ntxiv nrog rau cov khoom zais cia, fibroblasts tseem ua lub luag haujlwm hauv ECM tsim. ECM feem ntau yog lub luag haujlwm rau kev ncaj ncees ntawm cov ntaub so ntswg feem ntau thiab tswj cov protein thiab cell-specific thauj hauv vivo. Cov Cheebtsam ntawm ECM ua haujlwm li ligands rau cov cell nto receptors, xws li integrins, thiab tswj cov txheej txheem hauv nruab nrab ntawm homeostasis, suav nrog adhesion, apoptosis, proliferation, migration, survival, thiab sib txawv. ECM yog qhov muaj zog heev, tab tom hloov kho tsis tu ncua raws li kev tswj hwm ntawm qhov sib npaug ntawm qhov degradation thiab deposition. Kev poob ntawm cov ntaub so ntswg ECM kev ncaj ncees muaj ib qho ntawm cov cim ntawm kev mob qog noj ntshav, thiab nws txoj kev tswj hwm tsis zoo cuam tshuam nrog cov qog nqaij hlav thiab metastasis. ECM microenvironment sib txawv ntawm cov kab mob sib txawv vim muaj cov kev hloov pauv uas xav tau rau cov qauv hauv nruab nrog cev thiab kev ua haujlwm. Txawm hais tias muaj ntau haiv neeg ntawm ntau cov kab mob biochemical nyob rau hauv ECM microenvironment, heterogeneity nyob rau hauv nruj thiab elasticity kuj tau pom thoob plaws hauv lub cev, yam uas hloov pauv nrog lub hnub nyoog. Pathologically, ntau haiv neeg ntawm ligand qhia thiab txhav ua lub luag haujlwm tseem ceeb hauv kev mob qog nqaij hlav malignant.

Tumor immune microenvironment thiab aging:Lub cev tiv thaiv kab mob ua lub luag haujlwm tseem ceeb hauv kev lees paub thiab txo qis kev loj hlob ntawm cov ntaub so ntswg malignant. Yog li ntawd, kev khiav tawm ntawm lub cev tiv thaiv kab mob yog ib qho tseem ceeb hauv kev pib qog nqaij hlav, kev loj hlob, thiab metastasis. Ib qho ntawm cov cim tseem ceeb ntawm kev laus yog qhov nce qib qis hauv cov mob hnyav thoob plaws hauv lub cev, txheej txheem hu ua "mob". Cov lus teb tsis tu ncua no ua rau cov ntaub so ntswg degeneration thiab kev puas tsuaj ntawm cov mob hnyav thiab muaj feem cuam tshuam rau qhov induction thiab kev loj hlob ntawm cov qog malignant. Immunosenescence yog lwm yam uas ua rau muaj ntau yam kab mob uas muaj hnub nyoog. Muaj ntau yam cuam tshuam rau hauv cov txheej txheem no: atrophy ntawm thymus, kev hloov pauv ntawm qhov ntau thiab zoo ntawm T hlwb, thiab lwm yam. Kev mob tshwm sim los ua lub luag haujlwm tseem ceeb hauv kev ua kom ntau ntawm cov txheej txheem no, raws li cov kab mob inflammatory thiab cov lus teb cuam tshuam nrog qhov no. txheej txheem feem ntau yog inhibitory. Hnub nyoog-induced immune senescence tshwm sim feem ntau nyob rau hauv effector T cells thiab lwm yam kev tiv thaiv kab mob ntawm tes tseem ceeb heev rau qog kev tiv thaiv kab mob. Cov kev hloov pauv no tuaj yeem ua rau muaj kev ua kom muaj zog thiab nkag mus ntawm cov neeg muaj zog tiv thaiv kab mob ntau dua hauv cov neeg laus, uas tej zaum yuav yog qhov tseem ceeb rau lawv txoj kev mob qog noj ntshav thiab metastasis.

Cov txiaj ntsig ntawm ceg tcm: anti-aging & anti-tumor

Kev laus thiab Antineoplastic Drug Therapy Treatment Response Hauv kev kho cov neeg mob qog noj ntshav laus, kev txhawj xeeb txog kev noj qab haus huv muaj hnub nyoog txiav txim siab seb cov kev kho mob uas muaj txiaj ntsig zoo tuaj yeem siv yam xyuam xim ntawm cov koob tshuaj thiab txhim kho kev ciaj sia. Kwv yees li 50 feem pua ​​​​ntawm cov qog tshwm sim hauv cov neeg mob hnub nyoog 65 xyoos, tab sis cov ntaub ntawv soj ntsuam ntawm cov neeg mob hnub nyoog no muaj tsawg heev. Plaub caug feem pua ​​​​ntawm cov neeg mob cuv npe hauv kev sim tshuaj tiv thaiv kab mob antineoplastic muaj hnub nyoog tshaj 65 xyoo, thiab 10 feem pua ​​​​tau tshaj 75 xyoo. Qhov tseeb ntawm nws cov sawv cev ntawm lub hnub nyoog kho mob tiag tiag thaum pib ntawm feem ntau cov qog yog debatable. Targeted chemotherapy-induced acceleration of age-related hlav cov xwm txheej yuav muaj peev xwm pab kho mob, ua rau txo qis cytotoxicity thiab txhim kho kev ciaj sia. Hauv ntau qhov xwm txheej, kev siv tshuaj khomob rau cov neeg mob laus yog qhov ua tau zoo thiab ua kom muaj sia nyob ntev, tsis hais qhov chaw ntawm cov qog. Xav txog tias qhov chaw kho mob loj hauv kev txiav txim siab cov tshuaj khomob hauv cov neeg laus yog seb cov txiaj ntsig ntawm kev kho mob ntau dua cov kev mob tshwm sim, xav tau kev tshawb fawb ntxiv kom nkag siab zoo dua cov teebmeem cytotoxic ntawm qib molecular. Targeted therapy sawv cev rau tus qauv ntawm kev saib xyuas tus kheej, tsim los rau lub hom phiaj qog nqaij hlav, lossis TME, txhawm rau txhawb kev loj hlob ntawm tus kheej thiab kev loj hlob ntawm hom qog. Thaum muaj ntau tus neeg mob uas nws cov qog pib teb rau kev kho mob, feem ntau ua rau resistant. Muaj ntau cov kev tshawb fawb qhia tau hais tias kev hloov pauv ncaj qha hauv cov kev taw qhia hauv nruab nrab yog cuam tshuam nrog kev tiv thaiv kev kho mob; Txawm li cas los xij, kev sib raug zoo ncaj qha ntawm cov kev hloov pauv no thiab microenvironment tsis txhais tau zoo, tshwj xeeb tshaj yog nyob rau hnub nyoog. Cov phiaj xwm kev kho mob yuav muaj tsawg dua qhov tshwm sim ntawm kev siv tshuaj tua kab mob thiab kev siv hluav taws xob, thiab vim li ntawd, cov hlwb zoo li hloov pauv ntau yam, raws li kev hloov caj ces, kev hloov pauv ntawm epigenetic, thiab genomic instability, ua rau cov tshuaj tiv thaiv TME. Lub cev tiv thaiv kab mob thiab kev ua haujlwm hloov pauv ntau nrog lub hnub nyoog, thiab kev kho mob rau lub cev tiv thaiv kab mob ntawm cov neeg laus muaj kev cuam tshuam loj heev. Txawm li cas los xij, tseem muaj qee qhov kev tshawb fawb ncaj qha los ntsuas qhov ua tau zoo ntawm kev siv tshuaj tiv thaiv kab mob hauv cov laus cov qauv mob qog noj ntshav. Kev tshuaj xyuas qhov tob ntawm cov ntaub ntawv luam tawm tau qhia tias tam sim no muaj cov tshuaj tiv thaiv kab mob tiv thaiv kab mob muaj txiaj ntsig zoo rau cov neeg laus.

costanche txhim kho kev tiv thaiv kev laus microenvironment

Kev laus microenvironment yuav muaj kev cuam tshuam loj heev rau kev mob qog nqaij hlav. Cov hnub nyoog muaj feem cuam tshuam txog kev hloov pauv hauv stromal thiab kev tiv thaiv kab mob tuaj yeem ua rau cov qog nqaij hlav los ntawm lub xeev tsis meej lossis qeeb qeeb mus rau cov kab mob hnyav heev thiab metastatic.