Na gode da ziyartar Nature.com.Sigar burauzar da kuke amfani da ita tana da iyakacin tallafin CSS.Don ƙwarewa mafi kyau, muna ba da shawarar ku yi amfani da sabuntar burauza (ko kuma musaki Yanayin dacewa a cikin Internet Explorer).A halin yanzu, don tabbatar da ci gaba da goyan baya, za mu sanya rukunin yanar gizon ba tare da salo da JavaScript ba.
Toxoplasma gondii kwayar cuta ce ta intracellular protozoan parasite wanda ke daidaita microenvironment na mai cutar kuma an san yana da alaƙa da haɓakar haɓakar ƙwayar ƙwayar cuta.A cikin wannan binciken, mun yi hasashen cewa exosomal miRNA-21 daga kamuwa da cutar Toxoplasma yana haɓaka haɓakar ƙwayar ƙwayar cuta.Exosomes daga Toxoplasma-kamuwa da BV2 microglia an halicce su kuma an tabbatar da ciki na U87 glioma sel.Exosomal microRNA profiles an bincikar bayanan martaba ta hanyar amfani da tsararrun microRNA da microRNA-21A-5p masu alaƙa da Toxoplasma gondii da rarrabuwar ƙari.Mun kuma bincika matakan mRNA na kwayoyin da ke da alaƙa da ƙari a cikin ƙwayoyin glioma na U87 ta hanyar canza matakan miR-21 a cikin exosomes da tasirin exosomes akan haɓakar ƙwayoyin glioma na mutum U87.A cikin exosomes na U87 glioma Kwayoyin kamuwa da Toxoplasma gondii, an ƙara bayyanar da microRNA-21 da kuma aiki na antitumor genes (FoxO1, PTEN, da PDCD4) an rage.Abubuwan da aka samu BV2 sun kamu da Toxoplasma suna haifar da haɓakar ƙwayoyin glioma U87.Exosomes suna haifar da haɓakar ƙwayoyin U87 a cikin ƙirar ƙwayar cuta ta linzamin kwamfuta.Muna ba da shawarar cewa ƙara miR-21 na exosomal a cikin Toxoplasma-kamuwa da BV2 microglia na iya taka muhimmiyar rawa a matsayin mai haɓaka haɓakar tantanin halitta a cikin ƙwayoyin glioma U87 ta hanyar rage ƙayyadaddun kwayoyin antitumor.
An yi kiyasin cewa sama da mutane miliyan 18.1 na kamuwa da cutar sankara a duniya an gano su a cikin shekarar 2018, tare da kusan 297,000 na ciwace-ciwacen daji na tsakiya da aka gano a kowace shekara (1.6% na duk ciwace-ciwacen daji)1.Binciken da aka yi a baya ya nuna cewa abubuwan da ke haifar da ciwace-ciwacen kwakwalwar dan adam sun hada da sinadarai daban-daban, tarihin iyali, da ionizing radiation daga kayan aikin warkewa da na asibiti.Duk da haka, ba a san ainihin abin da ke haifar da waɗannan cututtuka ba.Kusan kashi 20 cikin 100 na duk cututtukan daji a duniya suna haifar da cututtukan cututtuka, gami da ƙwayoyin cuta, ƙwayoyin cuta da ƙwayoyin cuta3,4.Kwayoyin cututtuka masu yaduwa suna rushe tsarin kwayoyin halitta, kamar gyaran DNA da sake zagayowar tantanin halitta, kuma suna iya haifar da kumburi na kullum da lalacewa ga tsarin rigakafi5.
Kwayoyin cututtuka masu alaƙa da cutar kansar ɗan adam sune mafi yawan ƙwayoyin cuta, ciki har da ƙwayoyin cuta na papilloma na mutum da ƙwayoyin cutar hanta na B da C.Kwayoyin cuta kuma na iya taka rawar gani wajen haɓaka cutar kansar ɗan adam.Yawancin nau'in parasites, wato Schistosoma, Opishorchis viverrini, O. felineus, Clonorchis sinensis da Hymenolepis nana, sun shiga cikin nau'o'in ciwon daji na mutum 6,7,8.
Toxoplasma gondii shine protozoan intracellular wanda ke tsara microenvironment na ƙwayoyin cuta masu kamuwa da cuta.An kiyasta wannan kwayar cutar ta kama kusan kashi 30% na al'ummar duniya, wanda ke jefa daukacin al'ummar cikin hadari9,10.Toxoplasma gondii na iya cutar da gabobin jiki masu mahimmanci, gami da tsarin juyayi na tsakiya (CNS), kuma yana haifar da munanan cututtuka irin su cutar sankarau da kuma encephalitis, musamman a marasa lafiya marasa lafiya.Duk da haka, Toxoplasma gondii kuma na iya canza yanayin mahallin mai kamuwa da cuta ta hanyar daidaita haɓakar ƙwayoyin cuta da kuma amsawar rigakafi a cikin mutane marasa ƙarfi, wanda zai haifar da ci gaba da kamuwa da cutar asymptomatic na kullum9,11.Abin sha'awa, idan aka ba da alaƙa tsakanin yaduwar T. gondii da ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta a cikin vivo.
Exosomes an san su azaman masu sadarwa na intercellular waɗanda ke sadar da abun ciki na halitta, gami da sunadarai da acid nucleic, daga sel makwabta16,17.Exosomes na iya yin tasiri akan hanyoyin nazarin halittu masu alaƙa da ƙari kamar su anti-apoptosis, angiogenesis, da metastasis a cikin ƙananan ƙwayoyin cuta.Musamman, miRNAs (miRNAs), ƙananan RNAs marasa coding game da nucleotides 22 a tsayi, sune mahimman ka'idodin ka'idoji na bayanan rubutu waɗanda ke sarrafa sama da 30% na mRNA ɗan adam ta hanyar miRNA-induced silent complex (miRISC).Toxoplasma gondii na iya rushe hanyoyin nazarin halittu ta hanyar sarrafa maganganun miRNA a cikin rundunonin da suka kamu da cutar.MiRNAs mai masaukin baki sun ƙunshi mahimman sigina don daidaita hanyoyin nazarin halittu na rundunar don cimma dabarun rayuwa na parasite.Don haka, nazarin canje-canje a cikin bayanin martabar miRNA mai masaukin baki akan kamuwa da cuta tare da T. gondii zai iya taimaka mana mu fahimci hulɗar da ke tsakanin mai watsa shiri da T. gondii a fili.Hakika, Thirugnanam et al.15 ya nuna cewa T. gondii yana inganta ciwon daji na kwakwalwa ta hanyar canza maganganunsa a kan takamaiman miRNAs na rundunar da ke hade da ci gaban tumo kuma ya gano cewa T. gondii na iya haifar da gliomas a cikin dabbobin gwaji.
Wannan binciken yana mayar da hankali kan canjin exosomal miR-21 a cikin microglia mai watsa shiri wanda ya kamu da Toxoplasma BV2.Mun lura da yuwuwar rawar miR-21 da aka canza a cikin haɓakar ƙwayoyin glioma na U87 saboda riƙewa a cikin tsakiya na FoxO1/p27, wanda shine makasudin miR-21 mai wuce gona da iri.
Exosomes da aka samo daga BV2 an samo su ta amfani da centrifugation daban-daban kuma an inganta su ta hanyoyi daban-daban don hana kamuwa da cuta tare da sassan salula ko wasu vesicles.SDS-polyacrylamide gel electrophoresis (SDS-PAGE) ya nuna nau'i daban-daban tsakanin sunadaran da aka samo daga kwayoyin BV2 da exosomes (Figure 1A), kuma an kiyasta samfurori don kasancewar Alix, wanda aka bincika ta hanyar Yammacin Turai na alamun furotin exosomal a cikin .An samo lakabin Alix a cikin sunadaran exosome amma ba a cikin sunadaran lysate cell BV2 ba (Fig. 1B).Bugu da ƙari, an yi nazarin RNA da aka tsarkake daga abubuwan da aka samo daga BV2 ta amfani da na'urar nazarin halittu.18S da 28S ribosomal subunits ba a cika ganin su a cikin tsarin ƙaura na exosomal RNA ba, yana nuna ingantaccen tsafta (Hoto 1C).A ƙarshe, microscope na lantarki watsawa ya nuna cewa abubuwan da aka lura sun kasance kusan 60-150 nm a girman kuma suna da tsari mai kama da kofi na dabi'a na exosome ilimin halittar jiki (Fig. 1D).
Halayen exosomes da aka samo daga ƙwayoyin BV2.(A) Shafi na bayanan aminci.An ware sunadaran daga sel BV2 ko exosomes da aka samu daga BV2.Tsarin sunadaran suna bambanta tsakanin sel da exosomes.(B) Binciken ɓangarorin Yamma na alamar exosomal (Alix).(C) Ƙimar RNA da aka tsarkake daga ƙwayoyin BV2 da BV2 da aka samu exosomes ta amfani da na'urar nazarin halittu.Don haka, 18S da 28S ribosomal subunits a cikin ƙwayoyin BV2 ba a cika samun su a cikin RNA exosomal ba.(D) Microscope na lantarki mai watsawa ya nuna cewa exosomes keɓe daga sel BV2 an lalata su da 2% uranyl acetate.Exosomes suna da girman 60-150 nm a girman kuma mai siffa ta kofi (Song da Jung, bayanan da ba a buga ba).
An lura da ciki na cikin salula na exosomes da aka samu BV2 cikin ƙwayoyin glioma na mutum U87 ta hanyar amfani da microscopy.PKH26 masu lakabin exosomes suna cikin gida a cikin cytoplasm na sel U87.An lalata kwayoyin halitta tare da DAPI (Fig. 2A), yana nuna cewa BV2-samu exosomes na iya zama cikin ciki ta hanyar sel masu watsa shiri kuma suna tasiri yanayin yanayin sel masu karɓa.
Ciki na BV2-samu exosomes zuwa cikin U87 glioma Kwayoyin da BV2-samu exosomes kamuwa da Toxoplasma RH jawo yaduwa na U87 glioma Kwayoyin.(A) Exosomes wanda sel U87 suka mamaye da aka auna ta hanyar microscopy.Kwayoyin glioma na U87 an haɗa su tare da exosomes masu alamar PKH26 (ja) ko kuma ba tare da sarrafawa ba har tsawon sa'o'i 24.An lalata ƙwayoyin nuclei tare da DAPI (blue) sannan kuma an lura da su a ƙarƙashin ma'auni mai ma'ana (ma'auni: 10 μm, x 3000).(B) U87 glioma cell yadudduka an ƙaddara ta hanyar gwajin yaduwa ta tantanin halitta.Kwayoyin glioma U87 an bi da su tare da exosomes na lokacin da aka nuna. *P <0.05 an samu ta gwajin Student. *P <0.05 an samu ta gwajin Student. *P <0,05 получено по t-kритерию Стьюдента. *P <0.05 ta jarrabawar ɗalibi. *P <0.05 通过学生t 检验获得。 P <0.05 * P <0,05. * P <0.05 da aka samu ta amfani da t-gwajin Student.
Bayan tabbatar da ƙaddamar da abubuwan da aka samu na BV2 a cikin ƙwayoyin glioma na U87, mun yi gwaje-gwajen yaduwar kwayar halitta don bincikar rawar da BV2 da aka samu na Toxoplasma a cikin ci gaban kwayoyin glioma na mutum.Jiyya na U87 Kwayoyin da exosomes daga T. gondii-kamuwa BV2 Kwayoyin nuna cewa T. gondii-cutar BV2-samu exosomes haifar da muhimmanci mafi girma yaduwa na U87 Kwayoyin idan aka kwatanta da sarrafawa (Fig. 2B).
Bugu da ƙari, haɓakar ƙwayoyin U118 suna da sakamako iri ɗaya kamar U87, kamar yadda Toxoplasma ya motsa exosomes ya haifar da mafi girman matakan haɓaka (bayanan da ba a nuna ba).Dangane da waɗannan bayanan, zamu iya nuna cewa BV2-samu Toxoplasma-cutar exosomes suna taka muhimmiyar rawa wajen haɓakar ƙwayoyin glioma.
Don bincika tasirin Toxoplasma-infected BV2-samu exosomes a kan ci gaban ƙari, mun allura U87 glioma Kwayoyin a cikin tsirara mice ga wani xenograft model da allurar BV2-samu exosomes ko RH-cutar BV2-samu exosomes.Bayan ciwace-ciwacen ciwace ya bayyana bayan mako 1, kowane rukunin gwaji na beraye 5 an raba su gwargwadon girman ƙwayar cuta don sanin farkon farawa iri ɗaya, kuma an auna girman ƙari na kwanaki 22.
A cikin mice tare da samfurin U87 xenograft, an lura da girman girman ƙwayar ƙwayar cuta da nauyin nauyi a cikin BV2 da aka samu RH-cututtukan exosome a ranar 22 (Fig. 3A, B).A gefe guda, babu wani bambanci mai mahimmanci a cikin girman ƙwayar cuta tsakanin ƙungiyar exosome da aka samu ta BV2 da ƙungiyar kulawa bayan maganin exosome.Bugu da ƙari, ƙananan ƙwayoyin da aka yi musu allura tare da ƙwayoyin glioma da exosomes na gani sun nuna mafi girman ƙwayar ƙwayar cuta a cikin rukuni na RH da aka samu BV2-samu exosomes (Fig. 3C).Wadannan sakamakon sun nuna cewa BV2-samu Toxoplasma-cutar exosomes haifar da glioma girma a cikin wani linzamin kwamfuta model.
Oncogenesis (AC) na BV2-samu exosomes a cikin U87 xenograft linzamin kwamfuta model.Girman Tumor (A) da nauyi (B) sun karu sosai a cikin BALB/c tsiraicin berayen da aka bi da su tare da exosomes masu kamuwa da RH waɗanda aka samo daga BV2.BALB/c tsirara mice (C) an yi musu allurar subcutaneously tare da sel 1 x 107 U87 da aka dakatar a cikin cakuda Matrigel.Kwanaki shida bayan allura, 100 μg na exosomes da aka samo daga BV2 an bi da su a cikin mice.An auna girman Tumor da nauyi a kan kwanakin da aka nuna da kuma bayan sadaukarwa, bi da bi. P <0.05. P <0.05. *R <0,05. P <0.05. P <0.05. P <0.05. *R <0,05. P <0.05.
Bayanan sun nuna cewa 37 miRNAs (16 overexpressed da 21 downexpressed) da ke hade da rigakafi ko ci gaban ciwon daji an canza su sosai a cikin microglia bayan kamuwa da cuta tare da ƙwayar Toxoplasma RH (Fig. 4A).Matakan magana na miR-21 tsakanin miRNAs da aka canza an tabbatar da su ta hanyar RT-PCR na ainihi a cikin exosomes da aka samo daga BV2, exosomes da aka yi da ƙwayoyin BV2 da U87.Maganar miR-21 ya nuna karuwa mai yawa a cikin exosomes daga kwayoyin BV2 da suka kamu da Toxoplasma gondii (RH iri) (Fig. 4B).Matakan magana mai alaƙa na miR-21 a cikin ƙwayoyin BV2 da U87 sun ƙaru bayan ɗaukar sauye-sauyen exosomes (Fig. 4B).Matakan dangi na maganganun miR-21 a cikin kyallen kwakwalwa na marasa lafiya da ƙari da berayen da suka kamu da Toxoplasma gondii (irin ME49) sun fi girma fiye da sarrafawa, bi da bi (Fig. 4C).Waɗannan sakamakon sun daidaita tare da bambance-bambance tsakanin matakan magana na annabta da tabbatar da microRNAs a cikin vitro da in vivo.
Canje-canje a cikin maganganun exosomal miP-21a-5p a cikin microglia da ke kamuwa da Toxoplasma gondii (RH).(A) Yana nuna manyan canje-canje a cikin siRNA da ke da alaƙa da rigakafi ko ci gaban ciwace-ciwacen ƙwayar cuta ta T. gondii RH.(B) An gano matakan maganganun miR-21 na dangi ta hanyar RT-PCR na ainihi a cikin abubuwan da aka samu BV2, exosomes-magungunan BV2, da ƙwayoyin U87.(C) An samo matakan maganganun miR-21 na dangi a cikin kyallen kwakwalwa na marasa lafiya da ƙari (N=3) da mice da suka kamu da Toxoplasma gondii (ME49 iri) (N=3). *P <0.05 an samu ta gwajin Student. *P <0.05 an samu ta gwajin Student. *P <0,05 было получено с помощью t-критерия Стьюдента. An samo P <0.05 ta amfani da t-gwajin Student. *P <0.05 通过学生t 检验获得。 P <0.05 * P <0,05, полученный с помощью t-критерия Стьюдента. * P <0.05 da aka samu ta amfani da t-gwajin Student.
Exosomes daga ƙwayoyin BV2 masu cutar RH sun haifar da haɓakar gliomas a cikin vivo da in vitro (Fig. 2, 3).Don gano mRNAs masu dacewa, mun bincika matakan mRNA na kwayoyin cutar antitumor, akwatin cokali mai yatsa O1 (FoxO1), PTEN, da tsarin mutuwar kwayar halitta 4 (PDCD4) a cikin sel U87 da suka kamu da exosomes da aka samo daga BV2 ko RH BV2.Binciken bioinformatics ya nuna cewa wasu ƙwayoyin cuta masu alaƙa da ƙari, gami da FoxO1, PTEN, da PDCD4 genes, suna da wuraren ɗaure miR-2121,22.An rage matakan mRNA na kwayoyin da aka yi niyya na antitumor a cikin RH-cutar BV2-samu exosomes idan aka kwatanta da BV2-samu exosomes (Fig. 5A).FoxO1 ya nuna raguwar matakan furotin a cikin RH-cutar BV2-samu exosomes idan aka kwatanta da BV2-derived exosomes (Hoto 5B).Bisa ga waɗannan sakamakon, za mu iya tabbatar da cewa exosomes da aka samo daga RH-infected BV2 sun rushe kwayoyin anti-oncogenic, suna kula da rawar da suke da shi a ci gaban ƙwayar cuta.
Toxoplasma RH mai kamuwa da BV2-samu exosomes yana haifar da kashe kwayoyin antitumor a cikin U87 glioma Kwayoyin ta Toxoplasma RH-kamuwa da BV2-samu exosomes.(A) PCR na ainihi na FoxO1, PTEN da PDCD4 magana a cikin exosomes da aka samo daga T. gondii RH-infected BV2 idan aka kwatanta da PBS exosomes.An yi amfani da β-actin mRNA azaman sarrafawa.(B) An ƙaddara furcin FoxO1 ta hanyar lalatawar Yamma kuma an ƙididdige bayanan densitometry ta hanyar amfani da shirin ImageJ. *P <0.05 an samu ta gwajin Student. *P <0.05 an samu ta gwajin Student. *P <0,05 было получено с помощью t-критерия Стьюдента. An samo P <0.05 ta amfani da t-gwajin Student. *P <0.05 通过学生t 检验获得。 P <0.05 * P <0,05, полученный с помощью t-критерия Стьюдента. * P <0.05 da aka samu ta amfani da t-gwajin Student.
Don fahimtar tasirin miP-21 a cikin exosomes akan ƙa'idodin ƙwayoyin cuta masu alaƙa da ƙari, ƙwayoyin U87 an canza su tare da mai hana miP-21 ta amfani da Lipofectamine 2000 kuma an girbe ƙwayoyin 24 hours bayan canzawa.FoxO1 da p27 matakan magana a cikin sel da aka canza tare da masu hana miR-21 an kwatanta su da sel da aka yi amfani da su tare da exosomes BV2 da aka samu ta amfani da qRT-PCR (Fig. 6A, B).Canja wurin mai hana miR-21 zuwa cikin sel U87 ya ragu sosai da FoxO1 da magana p27 (FIG. 6).
RH mai cutar exosomal BV2-wanda aka samu miP-21 ya canza maganganun FoxO1/p27 a cikin ƙwayoyin glioma U87.An canza ƙwayoyin U87 tare da mai hana miP-21 ta amfani da Lipofectamine 2000 kuma an girbe sel sa'o'i 24 bayan canzawa.FoxO1 da p27 matakan magana a cikin sel da aka canza tare da masu hana miR-21 an kwatanta su da matakan da ke cikin sel waɗanda aka bi da su tare da exosomes da aka samu BV2 ta amfani da qRT-PCR (A, B).
Don guje wa amsawar rigakafi na mai masaukin baki, toxoplasma parasite ya canza zuwa ƙwayar nama.Suna parasitize nama daban-daban, ciki har da kwakwalwa, zuciya, da tsokar kwarangwal, a duk tsawon rayuwar mai masaukin kuma suna daidaita martanin garkuwar mai gida.Bugu da ƙari, za su iya daidaita tsarin tantanin halitta da apoptosis na kwayoyin halitta, suna inganta yaduwar su14,24.Toxoplasma gondii galibi yana cutar da ƙwayoyin dendritic, neutrophils, da layin monocyte/macrophage, gami da microglia na kwakwalwa.Toxoplasma gondii yana haifar da bambance-bambancen macrophages na M2 phenotype, yana shafar warkar da raunuka bayan kamuwa da cuta, kuma yana da alaƙa da hypervascularization da granulomatous fibrosis.Wannan halayen halayen ƙwayar cuta na Toxoplasma na iya zama alaƙa da alamomin da ke da alaƙa da ci gaban ƙari.Mahalli mara kyau da Toxoplasma ke tsara shi na iya kama da wanda ya dace da ciwon daji.Sabili da haka, ana iya ɗauka cewa kamuwa da cuta na Toxoplasma ya kamata ya ba da gudummawa ga ci gaban ciwan kwakwalwa.A gaskiya ma, an ba da rahoton yawan kamuwa da cutar Toxoplasma a cikin maganin marasa lafiya da ciwon kwakwalwa daban-daban.Bugu da ƙari, Toxoplasma gondii na iya zama wani nau'in ciwon daji kuma yana aiki tare don taimakawa wasu ƙwayoyin cuta masu cututtuka su bunkasa ciwan kwakwalwa.Game da wannan, ya kamata a lura cewa P. falciparum da Epstein-Barr cutar synergistically taimaka wajen samuwar Burkitt ta lymphoma.
An yi bincike sosai kan rawar da exosomes a matsayin masu tsarawa a fagen binciken ciwon daji.Koyaya, aikin exosomes tsakanin parasites da rundunonin da suka kamu da cutar ya kasance ba a fahimta sosai ba.Ya zuwa yanzu, hukumomi daban-daban, ciki har da sunadarai masu ɓoye, sun bayyana hanyoyin nazarin halittu waɗanda ƙwayoyin protozoan ke tsayayya da harin da aka yi da su da kuma ci gaba da kamuwa da cuta.Kwanan nan, an sami haɓakar ra'ayi cewa microvesicles masu alaƙa da protozoan da microRNAs ɗin su suna hulɗa tare da ƙwayoyin runduna don ƙirƙirar yanayi mai kyau don tsira.Don haka, ana buƙatar ƙarin karatu don gano alakar da ke tsakanin sauye-sauyen miRNAs exosomal da yaɗuwar ƙwayoyin glioma.Canjin MicroRNA (kwayoyin halittar miR-30c-1, miR-125b-2, miR-23b-27b-24-1 da miR-17-92) suna ɗaure ga mai tallata STAT3 a cikin macrophages ɗin ɗan adam da ke kamuwa da toxoplasma, an tsara shi kuma yana haifar da rigakafin. -apoptosis a mayar da martani ga Toxoplasma gondii kamuwa da cuta 29.Toxoplasma kamuwa da cuta yana ƙara bayyanar miR-17-5p da miR-106b-5p, waɗanda ke da alaƙa da cututtukan hyperproliferative da yawa 30.Waɗannan bayanan sun ba da shawarar cewa miRNAs mai masaukin da aka tsara ta hanyar kamuwa da cutar Toxoplasma sune mahimman kwayoyin halitta don tsira da ƙwayoyin cuta da kuma cututtukan ƙwayoyin cuta a cikin halayen halittu.
Canza miRNAs na iya yin tasiri iri-iri na ɗabi'a yayin farawa da ci gaban ƙwayoyin cuta, gami da gliomas: wadatar siginar girma, rashin hankali ga sigina masu hana girma, ƙauracewa apoptosis, yuwuwar kwafi mara iyaka, angiogenesis, mamayewa da metastasis, da kumburi.A cikin glioma, an gano miRNAs da aka canza a cikin binciken bayanan bayyanawa da yawa.
A cikin binciken da muke ciki, mun tabbatar da matakan miRNA-21 masu girma a cikin ƙwayoyin runduna masu kamuwa da toxoplasma.An gano miR-21 a matsayin ɗaya daga cikin microRNAs mafi yawan lokuta da aka wuce gona da iri a cikin ciwace-ciwacen ciwace-ciwace, gami da gliomas, 33 kuma bayanin sa yana da alaƙa da darajar glioma.Tara shaida yana nuna cewa miR-21 wani labari ne na oncogene wanda ke aiki azaman maganin anti-apoptotic a cikin ci gaban glioma kuma yana da yawa sosai a cikin kyallen takarda da plasma na cututtukan kwakwalwar ɗan adam.Abin sha'awa, rashin kunna miR-21 a cikin ƙwayoyin glioma da kyallen takarda yana haifar da hana yaduwar kwayar halitta saboda apoptosis mai dogaro da caspase.Binciken bioinformatic na miR-21 da aka annabta ya nuna ƙwayoyin cuta masu hana ƙari da yawa da ke da alaƙa da hanyoyin apoptosis, gami da shirye-shiryen mutuwar tantanin halitta 4 (PDCD4), tropomyosin (TPM1), PTEN, da akwatin cokali mai yatsa O1 (FoxO1), tare da miR-2121 daure wurin..22.38.
FoxO1, a matsayin daya daga cikin abubuwan da aka rubuta (FoxO), yana da hannu wajen haɓaka nau'ikan ciwon daji na ɗan adam kuma yana iya daidaita maganganun ƙwayoyin ƙwayoyin cuta kamar p21, p27, Bim, da FasL40.FoxO1 na iya ɗaure da kunna masu hana sake zagayowar tantanin halitta kamar p27 don murkushe haɓakar tantanin halitta.Bugu da ƙari, FoxO1 shine maɓalli mai mahimmanci na siginar PI3K / Akt kuma yana daidaita yawancin tsarin ilimin halitta kamar ci gaban sake zagayowar tantanin halitta da bambancin tantanin halitta ta hanyar kunna kwafin p2742.
A ƙarshe, mun yi imanin cewa exosomal miR-21 da aka samo daga Toxoplasma-cutar microglia na iya taka muhimmiyar rawa a matsayin mai kula da girma na ƙwayoyin glioma (Fig. 7).Koyaya, ana buƙatar ƙarin karatu don nemo hanyar haɗin kai kai tsaye tsakanin exosomal miR-21, canjin kamuwa da cutar Toxoplasma, da haɓakar glioma.Ana sa ran waɗannan sakamakon za su samar da wurin farawa don nazarin dangantakar dake tsakanin kamuwa da cutar Toxoplasma da abin da ya faru na glioma.
An gabatar da zane-zane na tsarin glioma (kwakwalwa) carcinogenesis a cikin wannan binciken.Marubucin ya zana a cikin PowerPoint 2019 (Microsoft, Redmond, WA).
Duk ka'idojin gwaji a cikin wannan binciken, gami da amfani da dabbobi, sun kasance daidai da Tsarin Kula da Dabbobi na Jami'ar Seoul da Ka'idodin Da'a na Kwamitin Mai amfani kuma Kwamitin Binciken Cibiyoyi na Makarantar Magunguna ta Jami'ar Seoul ta amince da shi (Lambar IRB SNU- 150715).-2).Dukkan hanyoyin gwaji an yi su daidai da shawarwarin ARRIVE.
BV2 linzamin kwamfuta microglia da U87 na ɗan adam glioma Kwayoyin an yi su a cikin Dulbecco's Modified Eagle's Medium (DMEM; Welgene, Seoul, Korea) da Roswell Park Memorial Institute's Medium (RPMI; Welgene), bi da bi, kowanne yana dauke da 10% fetal bovine serum, 4 mM l- glutamine, 0.2 mm penicillin da 0.05 mM streptomycin.An haɓaka ƙwayoyin sel a cikin incubator tare da 5% CO2 a 37 ° C.An yi amfani da wani layin salula na glioma, U118, don kwatanta da ƙwayoyin U87.
Don ware exosomes daga T. gondii-cutar RH da ME49, T. gondii tachyzoites (RH iri) an girbe daga cikin rami na ciki na 6-mako BALB / c mice allura 3-4 days kafin.An wanke tachyzoites sau uku tare da PBS kuma an tsarkake su ta hanyar centrifugation a cikin 40% Percoll (Sigma-Aldrich, St. Louis, MO, Amurka) 43.Don samun tachyzoites na iri ME49, BALB/c mice an allurar da su cikin peritoneally tare da 20 nama cysts da tachyzoite canji a cikin cysts an tattara ta hanyar wanke rami na ciki a ranar 6-8th bayan kamuwa da cuta (PI).Mice sun kamu da PBS.ME49 tachyzoites an girma a cikin sel wanda aka ƙara da 100 μg / ml penicillin (Gibco / BRL, Grand Island, NY, Amurka), 100 μg / ml streptomycin (Gibco / BRL), da 5% fetal bovine serum (Lonza, Walkersville, MD) .., Amurka) a 37 ° C da 5% carbon dioxide.Bayan noma a cikin ƙwayoyin Vero, ME49 tachyzoites an wuce sau biyu ta hanyar allurar ma'auni 25 sannan ta hanyar tace 5 µm don cire tarkace da sel.Bayan wankewa, an sake dakatar da tachyzoites a cikin PBS44.Nama cysts na Toxoplasma gondii iri ME49 an kiyaye su ta hanyar intraperitoneal allura na cysts ware daga kwakwalwa na C57BL / 6 mice kamuwa da cuta (Orient Bio Animal Center, Seongnam, Korea).An girbe kwakwalwar berayen da suka kamu da cutar ME49 bayan watanni 3 na PI kuma an niƙa su a ƙarƙashin na'urar hangen nesa don ware cysts.An adana berayen da suka kamu da cutar a ƙarƙashin yanayin marasa lafiya na musamman (SPF) a Makarantar Magunguna ta Jami'ar Seoul.
An fitar da jimlar RNA daga abubuwan da aka samo daga BV2, ƙwayoyin BV2 da kyallen takarda ta amfani da miRNeasy Mini Kit (Qiagen, Hilden, Jamus) bisa ga umarnin masana'anta, gami da lokacin shiryawa don matakin haɓakawa.An ƙaddara ƙaddamarwar RNA akan NanoDrop 2000 spectrophotometer.An tantance ingancin microarrays na RNA ta amfani da Agilent 2100 bioanalyzer (Agilent Technologies, Amstelveen, Netherlands).
DMEM tare da 10% exosome- matalauta FBS an shirya ta ultracentrifugation a 100,000g na 16 hours a 4 ° C kuma tace ta hanyar 0.22 µm tace (Nalgene, Rochester, NY, Amurka).Kwayoyin BV2, 5 × 105, an haɓaka su a cikin DMEM dauke da 10% exosome-depleted FBS da 1% maganin rigakafi a 37 ° C da 5% CO2.Bayan sa'o'i 24 na shiryawa, tachyzoites na damuwa RH ko ME49 (MOI = 10) an kara su a cikin sel kuma an cire kwayoyin cutar da ba su shiga cikin sa'a guda kuma an cika su da DMEM.Exosomes daga sel BV2 an keɓe su ta hanyar gyare-gyaren centrifugation na daban, hanyar da aka fi amfani da ita.Dakatar da pellet ɗin exosome a cikin 300 µl PBS don nazarin RNA ko furotin.An ƙaddara ƙaddamar da keɓancewar exosomes ta amfani da kit ɗin gwajin furotin BCA (Pierce, Rockford, IL, Amurka) da NanoDrop 2000 spectrophotometer.
Hazo daga sel BV2 ko exosomes da aka samo daga BV2 an lullube su a cikin maganin cire furotin na PRO-PREP ™ (iNtRon Biotechnology, Seongnam, Koriya) kuma an ɗora furotin a kan Coomassie mai haske shuɗi mai launin 10% SDS polyacrylamide gels.Bugu da ƙari, an canza sunadarai zuwa membranes na PVDF na 2 hours.An inganta ɓangarorin Yamma ta amfani da antibody Alix (Fasahar Siginar Kwayoyin salula, Beverly, MA, Amurka) azaman alamar exosomal.HRP-conjugated goat anti-mouse IgG (H + L) (Bethyl Laboratories, Montgomery, TX, Amurka) da LAS-1000 da luminescent image analyzer (Fuji Photographic Film, Tokyo, Japan) an yi amfani da matsayin sakandare antibody..An yi microscope na watsawa na lantarki don nazarin girman da yanayin halittar exosomes.Exosomes keɓe daga sel BV2 (6.40 μg / µl) an shirya su akan raga mai rufaffiyar carbon kuma an lalata su da 2% uranyl acetate na 1 min.An lura da samfuran da aka shirya a ƙarfin ƙarfin lantarki na 80 kV ta amfani da JEOL 1200-EX II (Tokyo, Japan) sanye da kyamarar ES1000W Erlangshen CCD (Gatan, Pleasanton, CA, Amurka).
Abubuwan da aka samo daga BV2 sun kasance masu lalata ta amfani da PKH26 Red Fluorescent Linker Kit (Sigma-Aldrich, St. Louis, MO, Amurka) na mintina 15 a dakin da zafin jiki.Kwayoyin U87, 2 × 105, tare da PKH26-labeled exosomes (ja) ko babu exosomes a matsayin mummunan iko, an sanya su a 37 ° C na 24 hours a cikin 5% CO2 incubator.U87 cell nuclei an stained tare da DAPI (blue), U87 Kwayoyin da aka gyarawa a cikin 4% paraformaldehyde for 15 min a 4 ° C sa'an nan aka bincika a cikin wani Leica TCS SP8 STED CW confocal tsarin microscope (Leica Microsystems, Mannheim, Jamus).abin lura.
An ƙirƙira cDNA daga siRNA ta amfani da Mir-X siRNA haɗin haɗin farko da SYBR qRT-PCR kit (Takara Bio Inc., Shiga, Japan).An yi PCR na ainihin lokacin ƙididdigewa ta amfani da tsarin ganowa na iQ5 na ainihi na PCR (Bio-Rad, Hercules, CA, Amurka) ta amfani da firamare da samfuri gauraye da SYBR Premix.An haɓaka DNA don hawan 40 na denaturation a 95 ° C na 15 s da annealing a 60 ° C na 60s.An yi nazarin bayanan kowane martani na PCR ta amfani da tsarin nazarin bayanai na iQ™5 software na tsarin gani (Bio-Rad).Canje-canje na dangi a cikin maganganun kwayoyin halitta tsakanin zaɓaɓɓun kwayoyin halitta da aka zaɓa da β-actin/siRNA (da U6) an ƙididdige su ta amfani da daidaitaccen hanyar lanƙwasa.Ana nuna jerin abubuwan da aka yi amfani da su a cikin Tebur 1.
3 x 104 U87 glioma Kwayoyin an shuka su a cikin faranti 96-rijiya kuma an haɗe su da ƙwayoyin cuta na Toxoplasma waɗanda aka samo daga BV2 (50 μg / ml) ko exosomes marasa ƙarfi waɗanda aka samo daga BV2 (50 μg / ml) azaman sarrafawa a 12, 18 da 36 hours. .An ƙaddara ƙimar haɓakar tantanin halitta ta amfani da Kit ɗin Ƙididdigar Ƙirar-8 (Dojindo, Kumamoto, Japan) (Ƙarin Ƙirar S1-S3) 46.
An sayi berayen BALB/c mace mai sati 5 tsirara daga Orient Bio (Seongnam-si, Koriya ta Kudu) kuma an ajiye su daban-daban a cikin kejin da bakararre a zazzabi na ɗaki (22± 2°C) da zafi (45±15°C).%) a dakin da zafin jiki (22± 2°C) da zafi (45± 15%).An yi zagayowar haske na sa'o'i 12 da zagayowar duhu na sa'o'i 12 a ƙarƙashin SPF (Cibiyar Dabbobin Dabbobi ta Jami'ar Seoul).An raba mice zuwa ƙungiyoyi uku na mice 5 kowannensu kuma an yi allurar da duk ƙungiyoyi tare da 400 ml na PBS mai ɗauke da ƙwayoyin glioma na 1 x 107 U87 da haɓakar haɓakar BD Matrigel ™ ( Kimiyyar BD, Miami, FL, Amurka).Kwanaki shida bayan allurar ƙwayar cuta, 200 MG na exosomes da aka samo daga ƙwayoyin BV2 (tare da / ba tare da kamuwa da cutar Toxoplasma ba) an yi musu allura a cikin wurin ciwon daji.Kwanaki ashirin da biyu bayan kamuwa da ciwon daji, an auna girman ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar kuma kuma an ƙididdige yawan ƙwayar ƙwayar cuta ta hanyar tsari: 0.5 × (nisa) × 2 × tsawon.
Binciken magana ta MicroRNA ta amfani da tsararrun miRCURYTM LNA miRNA, ƙarni na 7 yana da, mmu da rno arrays (EXIQON, Vedbaek, Denmark) wanda ke rufe kyawawan berayen 1119 tsakanin mutane 3100, linzamin kwamfuta da bera miRNA binciken kama.Yayin wannan hanya, an cire 250 zuwa 1000 ng na jimlar RNA daga 5'-phosphate ta hanyar jiyya tare da alkaline phosphatase na hanji na maraƙi wanda ya biyo baya tare da lakabin Hy3 kore mai kyalli.Samfuran da aka yi wa lakabin an haɗa su ta hanyar loda faifan microarray ta amfani da kayan aikin haɓaka ɗaki (Agilent Technologies, Santa Clara, CA, Amurka) da kayan faifan zane-zane (Agilent Technologies).An gudanar da haɓakawa na tsawon sa'o'i 16 a 56 ° C, sannan an wanke microarrays daidai da shawarwarin masana'anta.Sannan an duba zane-zanen faifan microarray da aka sarrafa ta amfani da tsarin na'urar daukar hoto na microarray Agilent G2565CA (Agilent Technologies).An shigo da Hotunan da aka bincika ta amfani da sigar software ta Agilent Feature Extraction 10.7.3.1 (Agilent Technologies) kuma an ƙididdige ƙarfin haske na kowane hoto ta amfani da fayil ɗin GAL daidai na ƙa'idar Exiqon da aka gyara.Ana adana bayanan microarray don binciken na yanzu a cikin bayanan GEO a ƙarƙashin lambar shiga GPL32397.
Bayanan bayanan balagagge na miRNAs exosomal a cikin microglia na RH ko ME49 damuwa da suka kamu da Toxoplasma an yi nazarin su ta amfani da kayan aikin cibiyar sadarwa daban-daban.An gano miRNAs masu alaƙa da haɓakar ƙari ta amfani da miRWalk2.0 (http://mirwalk.umm.uni-heidelberg.de) kuma an tace su tare da daidaitaccen ƙarfin siginar (log2) fiye da 8.0.Daga cikin miRNAs, miRNA da aka bayyana daban-daban an gano sun fi ninki 1.5 canzawa ta hanyar tantancewar tace miRNAs wanda nau'ikan RH ko ME49 suka kamu da T. gondii.
An tsara kwayoyin halitta a cikin faranti guda shida (3 x 105 Kwayoyin / rijiya) a cikin opti-MEM (Gibco, Carlsbad, CA, Amurka) ta amfani da Lipofectamine 2000 (Invitrogen, Carlsbad, CA, Amurka).Kwayoyin da aka canza sun kasance suna al'ada na tsawon sa'o'i 6 sannan aka canza matsakaici zuwa sabon matsakaici.An girbe sel sa'o'i 24 bayan canzawa.
An yi nazarin ƙididdiga musamman ta amfani da t-test Student tare da software na Excel (Microsoft, Washington, DC, Amurka).Don nazarin dabba na gwaji, an yi ANOVA ta hanyoyi biyu ta amfani da software na Prism 3.0 (GraphPad Software, La Jolla, CA, Amurka). P-darajar <0.05 an ɗauke su a matsayin mahimmancin ƙididdiga. P-darajar <0.05 an ɗauke su a matsayin mahimmancin ƙididdiga. Значения P <0,05 считались статистически значимыми. An yi la'akari da ƙimar P <0.05 a matsayin mahimmancin ƙididdiga. P 值< 0.05 被认为具有统计学意义。 P 值 <0.05 Значения P <0,05 считались статистически значимыми. An yi la'akari da ƙimar P <0.05 a matsayin mahimmancin ƙididdiga.
Dukkan ka'idojin gwaji da aka yi amfani da su a cikin wannan binciken an amince da su daga Hukumar Binciken Cibiyoyin Kula da Lafiya ta Jami'ar Kimiyya ta Jami'ar Seoul (Lambar IRB SNU-150715-2).
The data used in this study are available upon reasonable request from the first author (BK Jung; mulddang@snu.ac.kr). And the microarray data for the current study is deposited in the GEO database under registration number GPL32397.
Furley, J. et al.Kiyasin kamuwa da cutar kansar duniya da mace-mace a cikin 2018: tushen GLOBOCAN da hanyoyin.Tafsiri.J. Ruck 144, 1941-1953 (2019).
Rasheed, S., Rehman, K. & Akash, MS Hankali game da abubuwan haɗari na ciwace-ciwacen kwakwalwa da hanyoyin maganin su. Rasheed, S., Rehman, K. & Akash, MS Hankali game da abubuwan haɗari na ciwace-ciwacen kwakwalwa da hanyoyin maganin su.Rashid, S., Rehman, K. da Akash, MS Bita na abubuwan haɗari don ciwace-ciwacen kwakwalwa da manyan hanyoyin warkewa. Rasheed, S., Rehman, K. & Akash, MS 深入了解脑肿瘤的危险因素及其治疗干预措施。 Rasheed, S., Rehman, K. & Akash, MS Zurfafa fahimtar abubuwan haɗari na ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar kuma da kuma magani.Rashid, S., Rehman, K. da Akash, MS Bita na abubuwan haɗari don ciwace-ciwacen kwakwalwa da manyan hanyoyin warkewa.Kimiyyar halittu.Mai harhada magunguna.143, 112119 (2021).
Kato, I., Zhang, J. & Sun, J. Bacterial-viral interaction in the ordigestive tract cancers and female: Takaitacciyar shaida na cututtukan cututtuka da na dakin gwaje-gwaje. Kato, I., Zhang, J. & Sun, J. Bacterial-viral interaction in the ordigestive tract cancers and female: Takaitacciyar shaida na cututtukan cututtuka da na dakin gwaje-gwaje.Kato I., Zhang J. da Sun J. Mu'amalar kwayoyin cuta da kwayar cuta a cikin ciwon daji na gastrointestinal tract na ɗan adam da al'aurar mata: taƙaitaccen bayanan cututtukan cututtuka da na dakin gwaje-gwaje. Kato, I., Zhang, J. & Sun, J. 人类口腔消化道癌和女性生殖道癌中的细菌-病毒相互亡作用：腔消化道癌和女用 Kato, I., Zhang, J. & Sun, J. Bacterio-viral hulda a cikin jikin mutum cavity narkar da baki da kuma mata haihuwa fili: taƙaitaccen m cututtuka kimiyya da dakin gwaje-gwaje shaida.Kato I., Zhang J. da Sun J. Mu'amalar kwayoyin cuta da kwayar cuta a cikin ciwon daji na hanji na mutum da kansar al'aurar mata: taƙaitaccen bayanan cututtukan cututtuka da na dakin gwaje-gwaje.Ciwon daji 14, 425 (2022).
Magon, KL & Parish, JL Daga kamuwa da cuta zuwa ciwon daji: Ta yaya ƙwayoyin cutar ƙwayar cuta ta DNA ke canza ƙwayar carbon ta tsakiya da kuma metabolism na lipid. Magon, KL & Parish, JL Daga kamuwa da cuta zuwa ciwon daji: Ta yaya ƙwayoyin cutar ƙwayar cuta ta DNA ke canza ƙwayar carbon ta tsakiya da kuma metabolism na lipid.Mahon, KL da Parish, JL Cutar kamuwa da cutar kansa zuwa ciwon daji: yadda ƙwayoyin cuta na tushen DNA ke canza ƙwayar carbon ta tsakiya da metabolism na lipid. Magon, KL & Parish, JL 从感染到癌症：DNA Magon, KL & Parish, JL Daga kamuwa da cuta zuwa ciwon daji: yadda ƙwayoyin cuta na ƙwayoyin cuta na DNA ke canza ƙwayar carbon ta tsakiya da kuma metabolism na lipid.Mahon, KL da Parish, JL Wuta kamuwa da cuta zuwa ciwon daji: yadda ƙwayoyin cuta na ƙwayar cuta ta DNA ke canza carbon na tsakiya da metabolism na lipid a cikin sel.Bude Halittu.11, 210004 (2021).
Correia da Costa, JM et al.Catechol estrogens na schistosomes da ciwon hanta da ciwon daji mai alaƙa da helminth.gaba.zafi ciki.5, 444 (2014).