Tshooj Ib Transgelin-2 hauv Ntau Myeloma: Tus Cim Tshiab Ntawm Lub Raum Tsis Zoo

Abstract

Transgelin yog ib qho {{0}}kDa protein koom nrog hauv lub koom haum cytoskeletal thiab nthuav tawm hauv cov leeg nqaij. Raws li cov kev tshawb fawb tsiaj, nws yog ib tug muaj peev xwm nruab nrab ntawm lub raum raug mob thiab fibrosis, thiab nws lub luag hauj lwm nyob rau hauv tumorigenesis yog tshwm sim nyob rau hauv ntau yam mob qog noj ntshav. Txoj kev tshawb no suav nrog 126 cov neeg mob hauv lub tsheb thauj neeg mob uas muaj ntau yam myeloma (MM). Serum transgelin -2 concentrations tau ntsuas los ntawm enzyme-txuas immunoassay. Peb tau soj ntsuam cov kev koom tes ntawm lub hauv paus transgelin thiab lub raum kev ua haujlwm (cov ntshav creatinine, kwv yees glomerular filtration rate-eGFR, urinary markers of tubular raug mob: cystatin-C, neutrophil gelatinase-associated lipocalin-NGAL monomer, cell cycle arrest biomarkers IGFBP-7 TIMP-2) thiab cov cim ntawm MM lub nra. Baseline serum transgelin kuj tau soj ntsuam raws li kev kwv yees ntawm lub raum kev ua haujlwm tom qab ua raws li 27 lub hlis txij li pib ntawm txoj kev tshawb no. Cov kev sib raug zoo tseem ceeb tau raug kuaj pom ntawm cov ntshav transgelin {{10}} thiab ntshav creatinine (R=0.29; p=0). 001) thiab eGFR (R=−{45}}.25; p=0 007). Transgelin muaj kev sib raug zoo nrog cov roj ntsha tsis muaj lub teeb saws lambda (R=0.18; p=0.047) thiab cov ntshav periostin (R=−0.22; p=0.013) ), tom qab kev tshem tawm ntawm smoldering MM cov neeg mob. Cov neeg mob uas txo qis eGFR muaj cov qib transgelin ntau dua (qhov nruab nrab 106.6 piv rau 83.9 ng / mL), txawm hais tias qhov sib txawv yog qhov tseem ceeb (p=0.05). Txawm li cas los xij, lub hauv paus transgelin zoo sib raug zoo nrog cov ntshav creatinine tom qab lub sijhawm ua raws (R=0.37; p < 0.001) thiab tsis zoo cuam tshuam nrog eGFR tom qab lub sijhawm rov qab (R=−0.33; p <0.001). Tsis tas li ntawd, lub hauv paus siab dua cov ntshav hauv cov ntshav transgelin (beta=−0.11 ± 0.05; p=0.032)) tau kwv yees qis dua eGFR qhov tseem ceeb tom qab lub sijhawm ua raws, tsis hais txog lub hauv paus eGFR thiab lub sijhawm ua raws. Peb txoj kev tshawb fawb pom thawj zaug uas nce ntshav transgelin tsis zoo cuam tshuam nrog glomerular filtration hauv MM thiab kwv yees qhov kev poob qis hauv lub raum ua haujlwm ntev mus ntev.

Ntsiab lus

ntau yam myeloma; transgelin; tubular raug mob; biomarker.

Nyem qhov no kom tau txais cov teebmeem ntawm Cistanche

Taw qhia

According to the Global Burden of Disease 2016 study, the worldwide age-standardized incidence and death rate of multiple myeloma (MM) is estimated at 2.1 and 1.5 per 100,000 individuals, respectively. The highest incidence is observed in Australasia, North America, and Western Europe, while between 1990 and 2016, the number of new cases and deaths was increasing [1]. MM is a proliferative plasma cell disorder that is more prevalent in the aging population and presents itself with characteristic features of organ involvement: bone lesions, anemia, renal insufficiency, hypercalcemia, and specific malignancy biomarkers (plasma cell clonality ≥60%, involved to uninvolved serum free light chains (FLCs) ≥100 and >1 focal lesion ntawm magnetic resonance imaging) [2]. Cov ntaub ntawv pov thawj ntawm clonal plasma cell feem pua ​​​​ntawm ntau dua lossis sib npaug li 10 feem pua ​​​​ntawm cov pob txha pob txha lossis biopsy-proven plasmacytoma yog qhov tsim nyog los txhais cov ntaub ntawv ntawm MM [2]. Lub raum kev koom tes hauv MM yog ib txwm muaj (ze li ib feem plaub ntawm cov neeg mob) thiab tuaj yeem ua rau muaj qhov tsis zoo, tshwj xeeb tshaj yog tias lub raum ua haujlwm tsis zoo [3–5]. Lub raum tsis ua haujlwm tsis tshua muaj tsawg tab sis tuaj yeem muaj txog li 8 feem pua ​​​​ntawm cov neeg mob [3]. Lub raum tsis ua haujlwm hnyav yog ib qho mob hnyav uas muaj kev pheej hmoo ntawm kev tuag ntxov thiab yog ib qho ntawm cov neeg ua txhaum loj ntawm kev tuag ntxov [6,7]. Kev kho mob tsawg tsawg thiab qhov nruab nrab muaj sia nyob ntawm 3-4 lub hlis tau pom ua ntej qhov tshwm sim ntawm kev kho mob myeloma niaj hnub [8-10]. Cov lus teb tshuaj khomob thiab qhov hnyav ntawm lub raum tsis ua haujlwm yog qhov ua rau muaj kev ywj pheej ntawm kev muaj sia nyob, uas qhia txog qhov tseem ceeb ntawm kev kho mob thaum ntxov thiab muaj txiaj ntsig zoo rau lub hom phiaj ntawm plasma cell clone los tiv thaiv lub raum puas tsuaj [3]. Reversibility ntawm lub raum tsis ua hauj lwm tej zaum yuav yog ib qho tseem ceeb raws li cov lus teb rau chemotherapy nyob rau hauv cov nqe lus ntawm prognosis [9], txawm hais tias cov kev tshawb fawb tsis ntev los no tau pom tias txawm tias reversal tiav, cov txiaj ntsig tau qis dua rau cov neeg mob lub raum ua haujlwm ntawm lub hauv paus [11]. Lub raum tsis txaus yog suav tias yog thim rov qab li ntawm 50 feem pua ​​​​ntawm cov neeg mob hauv qee cov ntaub ntawv [8,9]. Nrog rau qhov tshwm sim ntawm cov tshuaj tshiab (xws li, proteasome inhibitors), qhov kev tshwm sim rau cov neeg mob MM uas lub raum tsis ua haujlwm tau zoo heev [7,11–16].

Hauv kev kho mob niaj hnub, kev soj ntsuam kev soj ntsuam ntawm lub raum ua haujlwm feem ntau yog nyob ntawm kev ntsuas cov ntshav creatinine siv los kwv yees tus nqi glomerular pom. Txawm li cas los xij, niaj hnub muaj kev ntsuas ntsuas (piv txwv li, ntshav creatinine) raug rau ntau qhov kev ceeb toom thiab tsis tas yuav tso cai rau kev kwv yees ntxov thiab txhim khu kev qha ntawm lub raum tsis tu ncua [17]. Serum creatinine concentrations yuav tsum tau txhais nrog rau kev paub txog confounding yam xws li (1) prerenal azotemia, (2) ntau lawm tus nqi nyob ntawm seb tus neeg thiab cov yam ntxwv kho mob, piv txwv li, hnub nyoog, poj niam los txiv neej, nqaij loj, thiab siv tshuaj, (3) lig sawv. txog li 72 teev tom qab raug mob, (4) loj "lub raum cia", thiab (5) cov kab mob sib kis (piv txwv li, sepsis, kab mob siab, mob leeg). Yog li, cov ntshav creatinine tsis tuaj yeem cuam tshuam qhov kev poob qis hauv glomerular pom. Novel biomarkers uas yuav pab cov kws kho mob hauv kev kwv yees kev raug mob raum thiab mob raum kev loj hlob yog qhov txaus siab heev. Kev tshawb fawb los txheeb xyuas lub raum raug mob (RI) cov neeg kho kom haum xeeb lossis cov cim hauv cov ntsiab lus tshwj xeeb ntawm myeloma tau lees paub raws li nws kuj tseem tuaj yeem pab txhawb kev tsim qauv, suav nrog cov txheej txheem pathophysiological sib txawv ua rau RI hauv cov neeg mob MM (ie, tubulitis vs glomerulonephritis).

Transgelin-2 (SM22), cytoskeletal actin-binding protein koom nrog kev sib txawv ntawm cov leeg nqaij du, osteoblasts, thiab adipocytes, muaj nyob rau hauv fibroblasts, qee lub hlwb epithelial, lub cev tiv thaiv kab mob (tsuas yog ib qho ntawm transgelin tsev neeg cov proteins. ), pob txha hlwb los yog qia hlwb [18]. Lub luag haujlwm tseem ceeb ntawm transgelin-2 yog kev koom tes hauv cytoskeleton remodeling los ntawm nws cov txiaj ntsig ntawm kev tswj hwm actin. Ntxiv mus, transgelin koom nrog hauv cov pob txha pob txha mesenchymal qia cell (MSC) proliferation thiab sib txawv. Cov kev tshawb fawb tsis ntev los no qhia txog qhov tsis zoo ntawm SM22 hauv cov kab mob sib txawv thiab hais txog nws lub luag haujlwm hauv kev mob qog noj ntshav thiab kev loj hlob. Raws li cov ntaub ntawv muaj, sib nrug los ntawm nws lub luag haujlwm oncogenic hauv cov qog nqaij hlav, SM22 tseem raug kho hauv cov kab mob leukemia thiab lymphoma cell kab thiab koom nrog hauv B-cell lymphoma kev loj hlob [19]. Interestingly, transgelin -2 overexpression tej zaum yuav txuam nrog chemotherapy resistance [20].

Tsis tas li ntawd, transgelin -2 tau pom tias yog ib qho cim ntawm interstitial fibrosis, glomerulosclerosis, thiab lub raum puas [21]. Nws txoj kev tswj hwm yog nyob ntawm etiology ntawm tus kab mob hauv ntau lub hlwb (glomerular parietal lossis visceral, lossis tubular interstitial hlwb), thiab cov lus qhia tau pom tau pom nyob rau hauv ob qho tib si glomerular thiab tubulointerstitial raug mob.

Peb txoj kev tshawb fawb tsom los soj ntsuam cov ntshav transgelin ua tus cim muaj peev xwm ntawm lub raum tsis zoo hauv cov neeg mob MM. Peb xav tias kev nce ntshav hauv cov ntshav ntawm transgelin tuaj yeem cuam tshuam nrog lub raum tsis ua haujlwm tsis txaus hauv tus kabmob no.

Cistanche hmoovthiabCistanche extract

Kev sib tham

Cov kev tshawb pom tsis ntev los no qhia tias transgelin tuaj yeem ua rau muaj peev xwm ua rau mob fibrosis thiab ua rau lub raum raug mob. Nws tau raug tshawb xyuas ntau yam kab mob raum [22–27]. Kev sim cov ntaub ntawv nyob rau hauv cov tsiaj qauv ntawm anti-glomerular qab daus daim nyias nyias nephritis qhia tau hais tias SM22 qhia yuav muaj kev cuam tshuam cov qauv thiab kev ua hauj lwm hloov tom qab raug mob. Kev txo qis ntawm cov kab mob podocyte tshwj xeeb thiab kev qhia ntawm transgelin tuaj yeem cuam tshuam txog kev sib txawv thiab kev hloov pauv ntawm qhov raug mob glomerular epithelium [24,26]. Nyob rau hauv cov qauv mob raum raug mob (5/6 nephrectomy) nrog kev raug mob thaum ntxov tubulointerstitial, SM22 qhia tau pom thaum ntxov ntawm lub peritubular thiab periglomerular compartments. Hauv kev teeb tsa ischemia-reperfusion, uas feem ntau cuam tshuam rau tubular epithelium, SM22 qhia tau raug sau tseg hauv peritubular interstitium [24]. Nyob rau hauv obstructive nephropathy qauv, periglomerular fibroblasts tau pom raws li cov thawj hlwb nrog transgelin up-txoj cai, nrog rau tom ntej nce nyob rau hauv interstitial fibroblasts [28]. Cov ntaub ntawv no qhia tau hais tias transgelin qhia nyob rau hauv ob qho tib si glomerular thiab tubulointerstitial raug mob, uas tsis txwv rau ib hom cell thiab suav hais tias yog ib qho kev qhia dav dav ntawm lub raum insult. Ua ke, cov ntaub ntawv no qhia tias nyob rau hauv lub voj voog ntawm kev raug mob, kho, thiab caws pliav ntawm lub raum cov ntaub so ntswg, transgelin tej zaum yuav yog ib qho cim qhia txog cov txheej txheem no.

Qhov kev tshawb pom tseem ceeb ntawm txoj kev tshawb fawb no yog kev sib raug zoo ntawm cov tshiab biomarker transgelin-2 thiab kev loj hlob ntawm lub raum tsis zoo tshaj qhov nruab nrab 21- hli kev soj ntsuam hauv cov neeg mob MM. Lub hauv paus siab dua hauv cov ntshav transgelin tau kwv yees qis dua eGFR los ntawm qhov kawg ntawm kev rov qab los, tsis hais txog hauv paus eGFR, qhov tso zis ntau ntawm cov cim raug mob (NGAL monomer thiab IGFBP-7), poj niam txiv neej, hnub nyoog, kev kho mob ua ntej, kev kho mob, thiab kev soj ntsuam ntev. Rau peb qhov kev paub zoo tshaj plaws, qhov no yog thawj txoj kev tshawb fawb soj ntsuam cov txiaj ntsig ntawm cov khoom siv tshiab no cuam tshuam nrog rau lub raum raug mob thiab nws cov koom haum nrog tsim cov ntsuas ntawm lub raum ua haujlwm hauv cov neeg mob MM ntawm ntau theem ntawm kev tswj hwm. Cov kev tshawb fawb yav dhau los tau tsom mus rau transgelin-2 qhov muaj peev xwm ntawm oncogenic thiab koom nrog MM hloov mus rau ntshav qog ntshav ntshav ntshav (PCL) uas hais txog transgelin-2 lub luag haujlwm ua tus cim ciaj sia tsis zoo [19]. Txawm li cas los xij, peb tsis muaj peev xwm ua pov thawj qhov kev koom tes ntawm cov ntshav transgelin concentrations thiab ciaj sia taus.

Thaum pib ntawm txoj kev tshawb no, ntshav transgelin sib raug zoo nrog cov ntshav creatinine thiab tsis zoo nrog eGFR. Txawm hais tias peb tau ntsuas cov zis ntau ntawm ob peb lub cim ntawm kev raug mob tubular, piv txwv li, NGAL monomer, cystatin C thiab cell cycle ntes biomarkers: TIMP-2 thiab IGFBP-7, peb tsuas pom muaj qhov tsis muaj zog ntawm kev sib raug zoo ntawm cov ntshav transgelin. thiab cov zis cystatin C. Tsis tas li ntawd, cov ntshav transgelin sib raug zoo nrog cov ntshav siab ntau ntawm FLC lambda (hom FLC feem ntau cuam tshuam nrog rau lub raum raug mob hauv MM). Cov ntaub ntawv tshawb fawb ntawm lub raum biopsies nyob rau hauv MM qhia txog heterogenous spectrum ntawm lub raum kab mob, nrog rau myeloma cast nephropathy (MCN) raws li feem ntau mob [17,18]. Kev sim ua pov thawj qhia tias FLCs ua lub luag haujlwm tseem ceeb hauv kev ua kom muaj kev hloov pauv ntawm cov kab mob thiab cov fibrotic nyob rau hauv lub raum compartment [29,30]. Cov qib siab ntawm FLCs hauv cov ntshav hauv qab no cov kab mob MM tshwj xeeb, uas tau muab txhais ua kev kho mob ntawm kev txo FLCs thiab rov ua rau lub raum zoo [31]. Cov ntaub ntawv qhia tias qhov kev tshawb pom ntawm lub raum tshwj xeeb kuj tseem cuam tshuam nrog kev tshwm sim hauv MM [32,33]. Kev tsim cov cam khwb cia thiab interstitial fibrosis, nrog rau tubular atrophy (IFTA), tau cuam tshuam rau lub raum rov qab hauv cov qauv sib txawv nrog rau cov xwm txheej hematological thiab cov yam ntxwv kho mob [33]. Cov yam ntxwv ntawm Histopathology (xws li IFTA) tau kawm yav dhau los nrog rau cov kev hloov pauv hauv kev kho mob hauv cov qauv kwv yees lub raum tsis ua haujlwm [34]. Nws tau raug hais tias qhov kev ntsuam xyuas thawj zaug tsis zoo rau hauv cov kab mob pathology, uas qhia txog qhov tseem ceeb ntawm lub raum biopsy thiab txhim khu kev qha biomarkers uas yuav pab tau rau hauv cheeb tsam (xws li, kev raug mob ntawm tubules, tubulointerstitial raug mob) thiab txhais tau qhov mob. Kev txheeb xyuas cov cim tshiab uas tuaj yeem cuam tshuam txog kev txhim kho neuropathology yog qhov txaus siab heev, vim nws tuaj yeem pab txhawb kev kuaj mob ntxov thiab tuaj yeem coj kev xaiv kho mob. Qhov zoo tshaj plaws, kev txhim kho ntawm cov cuab yeej uas tsis muaj kev cuam tshuam, tshwj xeeb rau cov kab mob sib txawv ntawm lub raum, tuaj yeem txhawb kev txiav txim siab txog kev kho mob thiab kev pheej hmoo stratification yav tom ntej.

Kev kuaj mob ntawm MM yog nyob ntawm kev txheeb xyuas hematological, feem ntau yog pob txha pob txha biopsy. Hauv kev xyaum kho mob, lub raum biopsy tsis yog ib txoj kev yuav tsum tau xaiv cov kev kho mob uas tsim nyog. Ua tib zoo xav txog qhov cuam tshuam ntawm lub raum biopsy, cov cim rau lub raum raug mob tej zaum yuav yog ib qho kev daws teeb meem zoo rau cov neeg mob MM. Txawm li cas los xij, peb qhov kev tshawb pom tseem ceeb yog kev sib koom ua ke ntawm cov hauv paus hauv cov ntshav transgelin thiab qhov kawg eGFR, uas qhia tau hais tias circulating transgelin concentrations kwv yees mus sij hawm ntev irreversible raum insufficiency nyob rau hauv cov neeg mob MM.

Hauv peb cov neeg mob nrog MM, ntshav transgelin tau nce siab dua, piv rau kev tswj hwm kev noj qab haus huv. Peb kuj tau pom ntau dua transgelin hauv cov txiv neej nrog MM, piv rau cov poj niam. Qhov sib txawv ntawm kev sib deev tsis tuaj yeem suav tias yog qhov sib txawv ntawm MM theem, lub raum ua haujlwm, lossis kev kho mob vim tias cov no tsis txawv ntawm cov txiv neej thiab poj niam (cov ntaub ntawv tsis qhia). Txawm li cas los xij, kev sib deev sib txawv hauv kev hloov pauv transgelin, tau tshaj tawm los ntawm lwm tus. Kev tsom xam proteomic ntawm tib neeg plasma luam tawm los ntawm Silliman li al. [35] qhia tawm 14-fold ntau dua transgelin concentration hauv txiv neej dua li poj niam. Cov kev tshawb fawb tsiaj kuj qhia txog qhov sib txawv ntawm kev sib deev hauv kev qhia ntawm transgelin [36]. Interestingly, nyob rau hauv peb pab pawg tswj trangelin theem siab dua nyob rau hauv cov poj niam. Peb tsis paub vim li cas rau qhov sib txawv ntawm kev sib deev sib txawv hauv kev nthuav dav transgelin concentrations, thiab cov kev tshawb fawb ntxiv yog tsim nyog los qhia cov hauv paus ntsiab lus.

Cistanche tubulosa

Transgelin koom nrog hauv cytoskeletal lub koom haum thiab kev cog lus [37] thiab nthuav tawm hauv cov leeg nqaij leeg [38,39]. Qhov no actin-binding protein tseem nyob rau hauv kev tshuaj xyuas txog kev mob qog noj ntshav cell proliferation, ntxeem tau, thiab metastases. Actin yog lub hauv paus tseem ceeb ntawm cytoskeleton uas koom nrog ntau yam haujlwm, thaum nws qhov kev tsis sib haum xeeb thiab kev hloov kho tshiab tau koom nrog hauv kev mob qog noj ntshav. Muaj peb hom transgelin proteins (hom 1, 2, thiab 3). Hom 2 muaj ntau nyob rau hauv cov leeg nqaij leeg thiab tau pib piav raws li SM22 . Transgelin-2 kev qhia tau tswj hwm hauv ntau cov qog nqaij hlav nrog nws cov staining siab dua hauv cov qog hlwb ntau dua li cov qog stroma. Ntxiv mus, transgelin{11}} koom nrog hauv cov pob txha pob txha mesenchymal qia cell (MSC) proliferation thiab sib txawv. Ntau cov kev tshawb fawb tau qhia txog kev hloov pauv hloov pauv hauv cov kab mob leukemia thiab lymphoma cell kab. Txawm hais tias transgelin{12}} overexpression tau cuam tshuam nrog kev kho tshuaj tiv thaiv, cov txheej txheem meej tsis paub. Raws li cov kev tshawb fawb yav dhau los, qhov overexpressed txawv txawv -2 noob tau pom nyob rau hauv methotrexate-resistant human choriocarcinoma cells thiab paclitaxel-resistant human cancer cells [20]. Transgelin-2 overexpression kuj tau txuas nrog kev pom tsis zoo, thiab transgelin{18}} tau raug npaj ua lub hom phiaj kho mob vim nws txwv cov qog hlwb (tsis sib xws rau hom transgelin-1) [40 ].

Qhov nrov tshaj plaws peb-tshuaj regimen siv nyob rau hauv MM kev kho mob muaj xws li ib tug proteasome inhibitor-bortezomib, thiab immunomodulatory tshuaj-lenalidomide thiab dexamethasone. Nyob rau hauv cov ntaub ntawv ntawm relapse los yog refractory MM, cov tshuaj tiv thaiv tsom rau cov hlwb myeloma (piv txwv li, daratumumab, elotuzumab, siltuximab, belantamab mandolin), nuclear export inhibitors (selinexor) los yog histone deacetylase inhibitors (panobinostat) yog siv. Ib qho tseem ceeb tshaj plaws ntawm cov tshuaj hloov pauv hauv MM yog proteasome inhibitor bortezomib, vim nws muaj ntau yam kev tiv thaiv myeloma cuam tshuam nrog rau kev cuam tshuam ntawm lub voj voog ntawm tes thiab induction ntawm apoptosis, kev hloov pauv ntawm cov pob txha pob txha microenvironment thiab inhibition ntawm nuclear factor kappa B (NFκB. ). Tus neeg sawv cev tshiab no txhim kho lub raum ua haujlwm thiab yuav tsum tau siv tshwj xeeb hauv pab pawg neeg mob uas muaj GFRs qis dua [41]. Tsis tas li ntawd, Bolomsky et al. pom muaj kev koom tes ntawm cov noob qhia theem ntawm ntau lub hom phiaj tshuaj immunomodulatory hauv cov pob txha pob txha mononuclear hlwb ntawm cov neeg mob MM thiab cov lus teb rau lenalidomide-dexamethasone regimen [42]. Interestingly, siab IKAROS protein ntau yog txuam nrog kev ua tau zoo ntawm cov neeg mob MM [42]. IKAROS kuj tau pom ntawm cov leeg nqaij leeg hauv cov hlwb renin hauv lub raum [43].

Hauv peb txoj kev tshawb fawb, cov neeg mob tau kho nrog ntau yam kev tswj hwm, feem ntau suav nrog lenalidomide (hauv 20 feem pua ​​​​ntawm cov neeg mob). Serum concentrations ntawm transgelin tsis txawv raws li cov tshuaj siv. Txawm hais tias peb tau pom ntau dua ntawm cov transgelin hauv cov neeg mob uas tsis tau txais kev kho mob MM ua ntej txoj kev tshawb fawb, hauv cov neeg uas tau kho yav dhau los tsis muaj kev sib raug zoo ntawm cov ntshav transgelin thiab cov kab mob uas tau txais. Tshwj xeeb, cov qib ntawm cov ntshav transgelin tsis txawv ntawm cov neeg uas tau txais lenalidomide thiab cov uas tsis tau. Lenalidomide modulates ntau yam ntawm lub cev tiv thaiv kab mob los ntawm kev sib cuam tshuam nrog cytokine ntau lawm los ntawm T-cell thiab NK cell tswj. Nws yog txuam nrog inhibition ntawm pro-inflammatory cytokines interleukin 6 thiab qog necrosis factor (TNF-). Tsis tas li ntawd, lenalidomide inhibits MM hlwb thiab lawv cov kev cuam tshuam, ua rau apoptosis [44]. Hauv peb txoj kev tshawb fawb, tsis muaj kev sib raug zoo ntawm cov ntshav qab zib interleukin 6 thiab qib transgelin hauv cov neeg mob MM (R=0.09; p=0.4). Xav tias tsuas yog 25 tus neeg mob tau txais lenalidomide thaum pib ntawm peb txoj kev tshawb fawb, peb tsis tuaj yeem ntseeg tau tias tsis suav nrog cov tshuaj tsis muaj zog mus rau nruab nrab ntawm cov tshuaj (lossis lwm yam tshuaj tiv thaiv MM) ntawm cov ntshav transgelin concentrations. Txij li thaum transgelin qhia tau kawm tsuas yog ib qho overexpressed molecule nyob rau hauv MM hloov mus rau PCL, yav tom ntej kev tshawb fawb yuav tsum qhia lub luag hauj lwm ntawm transgelin nyob rau hauv txoj kev loj hlob ntawm MM thiab yuav ua li cas nws yuav cuam tshuam los ntawm MM kev kho mob.

Although smoldering MM (SMM) patients have a normal renal function defined as GFR >60 mL / min / 1.73 m2, peb pom tau nce siab txawv -2 cov ntshav ntshav ntau hauv pawg no. Qhov kev tshawb pom no tuaj yeem muaj cov lus piav qhia pathophysiological. Kev tswj hwm ntawm transgelin-2 tau cuam tshuam nrog qog nqaij hlav thiab mob qog noj ntshav thiab yuav txawv nrog rau theem kho mob thiab qog loj. Interestingly, ob peb cov kev tshawb fawb qhia ntau dua ntawm transgelin -2 nyob rau hauv o (piv txwv li, SIRS) thiab tshawb SM22 overexpression nyob rau hauv cov kev cai ntawm NIK transcription thiab proinflammatory NF-kB-signaling pathways raws li ib tug modulator ntawm vascular o [20,45 ]. Cov kev tshawb fawb no qhia tias transgelin tuaj yeem raug saib raws li kev tiv thaiv kab mob. Ua tib zoo xav txog lub luag haujlwm ntawm interleukin 6 hauv MM pathogenesis raws li kev loj hlob thiab muaj sia nyob, inhibiting apoptosis hauv myeloma hlwb, qhov no kuj tseem tuaj yeem piav qhia SM22 lub luag haujlwm hauv cov qog nqaij hlav. Qhov no tuaj yeem txhawb qhov kev xav tias thaum pib ntawm tus kab mob thiab qog nqaij hlav, transgelin{15}} ntau dua. Txawm li cas los xij, ob peb tsab ntawv qhia tau pom tias transgelin{16}} inhibits motility ntawm cov qog nqaij hlav cancer los ntawm suppressing actin polymerization. Ntxiv mus, raws li cov ntaub ntawv muaj, tsuas yog 2 feem pua ​​​​ntawm cov neeg mob SMM tsim MM. Tsis tas li ntawd, ntau dua ntawm transgelin hauv peb cov neeg mob nrog SMM tuaj yeem cuam tshuam nrog qhov tseeb tias lawv tsis tau txais kev kho mob. Transgelin qib kuj tseem siab dua hauv cov neeg mob uas tsis tau txais kev kho mob MM ua ntej txoj kev tshawb fawb. Ntxiv mus, kev sib deev ntawm cov neeg mob nrog SMM tuaj yeem ua lub luag haujlwm hauv kev nce siab ntawm transgelin -2 concentrations xws li hauv pawg neeg kawm transgelin concentrations siab dua rau cov txiv neej, thiab SMM / cov neeg mob tsis kho feem ntau yog txiv neej. Txawm li cas los xij, vim peb tsis tuaj yeem txheeb xyuas cov ntaub ntawv dhau los ntawm transgelin hauv cov neeg mob nrog SMM, thiab cov neeg mob SMM hauv peb txoj kev tshawb fawb tsawg heev, peb tsuas yog xav txog qhov kev tshawb pom no.

Cov txiaj ntsig Cistanche

Muaj ntau qhov kev txwv ntawm qhov kev tshawb fawb tam sim no uas yuav tsum tau hais txog. Ua ntej, pab pawg tshawb fawb yog cov qauv sib txawv ntawm cov neeg mob los ntawm qhov chaw kho mob sab nraud. Qhov sib txawv ntawm tus kheej thiab tus yam ntxwv ntawm tus kab mob tuaj yeem npog qhov kev sib raug zoo ntawm transgelin -2 nrog rau lub raum kev koom tes. Tsis tas li ntawd, tsis muaj cov qauv kuaj ntsuas ntsuas los ntsuas transgelin concentrations. Txawm hais tias peb tau muab cov ntaub ntawv ntawm cov ntshav transgelin hauv ib pawg me me ntawm cov neeg noj qab haus huv, cov ntaub ntawv no yuav tsum raug suav tias yog ib ntus. Transgelin-2 tau kawm tsis tshua muaj nyob hauv MM thiab nkag siab txog nws lub luag haujlwm thiab qhov chaw muaj peev xwm ua tus cim ntawm lub raum raug mob yuav tsum muaj qhov sib txawv ntawm qhov loj ntawm cov molecule hauv kev ncig. Cov kev tshawb fawb tom ntej no yuav tsum tshawb xyuas cov qauv ntawm lub raum biopsy los qhia txog kev sib koom ua ke ntawm transgelin thiab ntau hom mob raum raug mob hauv MM thiab yuav tsum tau lees paub peb qhov kev tshawb pom hauv kev sib piv nrog rau lub raum kev koom tes thiab kev tswj cov pej xeem.

Cov ntaub ntawv

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Karolina Woziwodzka 1 , Jolanta Małyszko 2 , Ewa Koc-˙Zórawska 3 , Marcin ˙Zórawski 4 , Paulina Dumnicka 5 , Artur Jurczyszyn 6 , Krzysztof Batko 1 , 5 Paulina Mazur nowski 1, Paulina Gołasa 1, Jacek A . Małyszko 7 , Ryszard Dro˙zd˙z 5 and Katarzyna Krzanowska 1,

1 Lub Rooj Sib Tham thiab Lub Tsev Haujlwm ntawm Nephrology, Jagiellonian University Medical College, 30-688 Kraków, Poland; woziwodzka.karolina@gmail.com (KW); batko.krzysztof@gmail.com (KB); mbanaszkiewicz92@gmail.com (MB); mkrzanowski@op.pl (MK); paulinagolasa1@gmail.com (PG)

2 Department of Nephrology, Dialysis thiab Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland; jolmal@poczta.onet.pl

3 Second Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, 15-276 Bialystok, Poland; ewakoczorawska@wp.pl

4 Department of Clinical Medicine, Medical University of Bialystok, 15-254 Bialystok, Poland; mzorawski@wp.pl

5 Department of Medical Diagnostics, Jagiellonian University Medical College, 30-688 Kraków, Poland; paulina.dumnicka@uj.edu.pl (PD); paulina.pater@uj.edu.pl (PM); ryszard.drozdz@uj.edu.pl (RD)

6 Lub Rooj Tswjhwm Saib Xyuas Hematology, Jagiellonian University Medical College, 31-501 Kraków, Poland; mmjurczy@cyf-kr.edu.pl

7 Thawj Lub Tsev Haujlwm ntawm Nephrology thiab Transplantology nrog Dialysis Unit, Medical University of Bialystok, 15-540 Bialystok, Poland; jacek.malyszko@umb.edu.pl