Inqaku
I-methylene blue nobomi obude: iiseli, izilwanyana, nobungqina ebantwini
I-methylene blue ayikaboniswa ukuba yandisa ubude bobomi babantu kuphando olufunyenwe kolu phononongo. Ezinye iziphumo zaselebhu zinento yokwenza nokuguga, kodwa iziphumo ezilinganisiweyo zahluke kakhulu: iiseli eziqhubeka nokwahlukana, iimpuku ezisinda zide zibe mdala, nabantu abagqiba umsebenzi wokuvavanya inkumbulo ziziphumo ezahlukeneyo.
Ngoko owona mbuzo uluncedo ngulo ucacileyo: yintoni ephile ixesha elide ngakumbi, phantsi kweziphi iimeko, yaye bulinganiswe njani ubomi obude? Impendulo inqanda indlela yokusebenza ethembisayo ekubeni ijike ibe libango leminyaka eyongezelelweyo yobomi babantu.
Iintsingiselo ezine zebango lokulwa nokuguga
- Ukuguga kweeseli: imeko apho iiseli ziyeka ukwahlukana zize zibe nolunye utshintsho. Ukulibazisa le meko kwiiseli ezikhuliswa elebhu kwahlukile ekususeni iiseli esele zigugile.
- Ubude bobomi: ixesha into ephilayo ehlala iphila ngalo. Uphononongo lokusinda lulandelela izilwanyana okanye abantu, kuquka ukusweleka kwabo, kunokuba lulinganise iiseli zabo kuphela.
- Ixesha lokuphila usempilweni: ixesha eliphilwa ngoxa impilo namandla okwenza imisebenzi egciniwe. Uvavanyo lwesakhiwo samathambo okanye lwamandla omzimba lunokunika ulwazi ngenxalenye enye yeli xesha ngaphandle kokubonisa ukusinda ixesha elide ngakumbi.
- Ubudala bebhayoloji: uqikelelo oluphuma kwimilinganiselo ekhethiweyo. Utshintsho kolo qikelelo sisiphumo esilinganisiweyo ngokwaso, hayi ukuqaphela ukuba umntu uphile iminyaka eyongezelelweyo.
Inqaku lophando linokuba bubungqina obomeleleyo kwelinye lala mabango lize linike ubungqina obuncinane kwelinye. Isishwankathelo sobungqina beenzuzo ebantwini sisebenzisa lo mahluko kwamanye amabango nge-methylene blue.
Oko kuboniswa luphando lweeseli
Kulinge lika-Atamna noogxa bakhe ngeefibroblast, i-methylene blue eyongezwa kwisondlo sokukhulisa iiseli yalibazisa ukuguga kweefibroblast zemiphunga yabantu ze-IMR90. Abaphandi banike ingxelo yokuba inani leeseli liphindeke kabini ngaphezu kwamaxesha angama-20 ongezelelweyo xa kuthelekiswa neeseli zothelekiso. Iiseli ezikhuliswayo zazibalwa ngokuphindaphindiweyo zize ziphinde zifakwe kwisondlo esitsha, ngoko “ubude bobomi” babuchaza amandla azo okuqhubeka nokwanda.
Ukuphindeka kabini kwenani leeseli kuthetha ukuba inani leeseli liphinda kabini. Ukuphindeka kabini okungama-20 ongezelelweyo akuthethi iminyaka engama-20 eyongezelelweyo, okanye ukwanda nge-20% kobude bobomi bomntu ezinikelwe kuye iiseli. Eli linge likwalinganise utshintsho kwiimitochondria, lixhasa ingcamango yebhayoloji ngaphandle kokumisela ukuba umzimba uphela uyahlaziyeka. Indlela amalinge eefibroblast alinganisa ngayo ukuguga kweeseli ichaza umahluko phakathi kokwanda kweeseli nokususwa kweeseli ezigugileyo.
Inqaku lesibini elidla ngokucatshulwa laphonononga imodeli yesifo esithile. Uphando luka-Xiong noogxa bakhe ngeprogeria lwafaka iifibroblast zabantu abanesifo se-Hutchinson-Gilford progeria syndrome kwisondlo sokukhulisa iiseli esine-methylene blue. Izinto ezingaqhelekanga kwiinucleus nakwiimitochondria zaphucuka; ukukhula kwalandelelwa kangangeeveki ezili-12, eminye imilinganiselo ithathwa ngamaxesha amafutshane kunoko.
Ezi yayiziiseli ezivela ebantwini, hayi abantu abathatha inxaxheba kunyango. Esi sifo sibandakanya iproteni yeprogerin engaqhelekanga, ngoko ukuphucula ezo mpawu zeeseli akumisi ukuba kukho unyango lweprogeria okanye impembelelo ngokubanzi ekugugeni kwabantu abasempilweni. Inkcazelo yemodeli yeeseli zeprogeria igubungela loo mbuzo wophando unomda omncinane. Iziphumo zokuthambisa nezokufakwa esikhumbeni zikwiphononongo lobungqina bokhathalelo lwesikhumba elahlukileyo.
Amanqanaba obungqina: into ephilayo, isiphumo esilinganisiweyo, nexesha
Funda usihla kula manqanaba usiya kumbuzo wobomi obude babantu. Ukusondela ngakumbi kuloo mbuzo akuqinisekisi isiphumo esihle. Umqolo ngamnye uchaza oko kwaqatshelwa ngokwenene.
| Inqanaba lobungqina nophononongo | Imodeli nokuchanabeka | Ixesha | Isiphumo esilinganisiweyo nokutolikwa kwaso |
|---|---|---|---|
| 1. Ukuguga kweeseli ngokwahlukana | Iifibroblast zabantu ze-IMR90; i-methylene blue kwisondlo sokukhulisa iiseli xa kuthelekiswa neeseli ezinganyangwanga | Ukuchanabeka okuqhubekayo ngokudluliselwa kweeseli ngokulandelelana veki nganye de zigugile | Ukuphindeka kabini kwenani leeseli nemilinganiselo yeemitochondria; ubude bexesha lokwanda kweeseli bandisiwe |
| 1. Utshintsho lweeseli olunxulumene nesifo | Iifibroblast eziqhelekileyo nezeprogeria; ukuchanabeka kwi-100 nM kwisondlo sokukhulisa iiseli xa kuthelekiswa nesithwala-sithako sodwa kulinge lokukhula olukhankanyiweyo | Ukukhula kulandelelwe kangangeeveki ezili-12; iimvavanyo ezikhethiweyo zeemitochondria neenucleus kwiiveki ezi-5–8 | Ukukhula nesakhiwo seeseli; akukho siphumo sokusinda kwezigulana silinganisiweyo |
| 2. Ukusinda kwesilwanyana siphela | Iimpuku ze-UM-HET3 eziyindoda nezizimazi; i-methylene blue hydrate ekutyeni xa kuthelekiswa nokutya kothelekiso | Ukususela kubudala beenyanga ezi-4 kuqhubeke nokulandelela ubude bobomi | Akukho nzuzo ibalulekileyo ngokwezibalo kubude bobomi obuphakathi kwidatha edityanisiweyo; ubude bobomi kwipesenti yama-90 yeemazi banda nge-6% |
| 3. Icandelo lokusebenza elinxulumene nokuguga | Iimpuku ezizimazi ze-C57BL/6J ezineenyanga ezili-18; i-methylene blue emanzini okusela xa kuthelekiswa namanzi aqhelekileyo | Iinyanga ezi-6 okanye ezili-12 | I-micro-CT yamathambo; akukho khuselo ekulahlekeni kwamathambo okunxulumene nobudala |
| 4. Ilinge lexesha elifutshane ebantwini | Abantu abadala abangama-26 abasempilweni; ukunikwa i-methylene blue ngomlomo kube kanye xa kuthelekiswa neplacebo | Uvavanyo ngaphambi kokunikwa nasemva kweyure e-1 | Ukusebenza kwengqondo okunxulumene nomsebenzi nokusebenza kwenkumbulo; akukho mlinganiselo wobude bobomi okanye wexesha elide lokuphila usempilweni |
Ubuninzi besithako neendlela esifakwe ngazo zichonga amalinge. Aziniki sicwangciso sokusetyenziswa ngenjongo yobomi obude babantu. Ngokukodwa, ukongeza ikhemikhali ngqo kwisondlo seeseli kudlula ekufunxweni, ekusasazweni nasekukhutshweni kwayo emzimbeni opheleleyo. Ithala lophando lihlela izifundo ngokwezi nkcukacha zoyilo.
Kutheni isiphumo seempuku sidinga imilinganiselo emibini yobude bobomi
Uphononongo lwe-Interventions Testing Program olwenziwa kwiindawo ezintathu lwasebenzisa iimpuku ezahlukahlukeneyo ngokwemfuza. Iindlela zalo zichaza i-28 mg ye-methylene blue hydrate ngekilogram yokutya; icandelo leziphumo linika i-27 mg/kg ekutyeni. Zombini zichaza ubuninzi besithako ekutyeni, hayi iimiligram ngekilogram yobunzima bomzimba.
Iigrafu zokusinda zedatha edityanisiweyo azizange ziphucuke ngendlela ebalulekileyo ngokwezibalo nakwesiphi na isini. Kodwa kwiimazi, ubude bobomi kwipesenti yama-90 banda ukusuka kwiintsuku ezi-1,072 ukuya kwezi-1,138, malunga ne-6%, nge-P = .004. Abaphandi abazange bazithathe iziphumo zizonke njengezaneleyo ukuxhasa inyathelo elisebenzayo lokulwa nokuguga kwinqanaba lokuchanabeka elavavanywayo.
Ubude bobomi obuphakathi bubudala apho isiqingatha seqela sele sifile. Ubude bobomi kwipesenti yama-90 buchaza isiphelo sabadala kakhulu kuluhlu, apho malunga nama-90% sele efile. Apha, “obona bude bobomi bukhulu” bubhekisa kuloo mlinganiselo usekelwe kwipesenti, hayi kubudala besilwanyana esinye esaphule irekhodi. Inyathelo lingachaphazela inxalenye enye yolwabiwo lokusinda ngaphandle kokuphucula umbindi walo. Isiphumo esifumaneka kwizilwanyana ezizimazi kuphela naso asinakumisela ukuba kukho inzuzo kubasetyhini.
Ixesha lokuphila usempilweni kufuneka livavanywe ngokwahlukileyo
Ilinge lika-2024 lokuguga kwamathambo libonisa ukuba kutheni indlela yokusebenza inganelanga. Nangona kwakukho isizathu sokujolisa ekungasebenzini kakuhle kweemitochondria, i-methylene blue ayizange ithintele ukulahleka kwamathambo kwiimpuku ezizimazi ezindala eziyifumene emanzini okusela. Ilinge elahlukileyo kwakwelo nqaku nalo alifumananga khuselo lwamathambo xa iimpuku ezahlukahlukeneyo ngokwemfuza zichanabeke kuyo ngokutya.
Oku akungqineli ukuba zonke iziphumo ezinokubakho ekusebenzeni azichaphazeleki. Kodwa kubonisa ukuba isiphumo esihle kwiiseli ezikhuliswa elebhu asinakucingelwa ukuba sikhusela ilungu lomzimba eligugayo. Uphononongo lobungqina bokuguga kwamathambo luhlolisisa nzulu loo ngxaki yokudlulisela iziphumo kwimeko eyahlukileyo.
Oko kunokumiselwa ziimvavanyo ebantwini neengxelo zobuqu
Uphononongo lokuthatha imifanekiso ebantwini ababelwe amaqela ngokungakhethiyo lwahlolisisa impendulo yexesha elifutshane emva kokunikwa ngomlomo. Alunakuphendula ukuba ukuchanabeka okuphindaphindiweyo kugcina ukukwazi ukuzimela, kuthintela izifo ezinxulumene nobudala, okanye kwandisa ukusinda kwiminyaka emininzi. Iyeza linokuba nempembelelo elinganisiweyo yexesha elifutshane ngaphandle kokuphucula nayiphi na kwezo ziphumo.
Ingqiqo efanayo isebenza kwiimvavanyo zobudala bebhayoloji. Nokuba amanqaku ayehla emva kokuba umntu eqalise i-methylene blue, oko kuqatshelweyo kumisela utshintsho lwamanqaku. Ukubonisa inzuzo yokusinda kufuna ubungqina bokuba inyathelo liphucula ukusinda, okanye umlinganiselo obambele ukusinda oqinisekiswe ngokungqongqo kolo nyango nakwelo qela labantu. Amanqaku aqikelela umngcipheko kubantu abahlukeneyo awabonisi ngokuzenzekelayo ukuba ukuwatshintsha kutshintsha loo mngcipheko.
Iingxelo zobuqu ezibandakanya amanyathelo amaninzi zinengxaki eyongezelelweyo. Ukuba umntu utshintsha ukutya, umthambo, ukulala, izongezelelo ezininzi, ne-methylene blue ngaxeshanye, ukuphucuka okulandelayo akunakwahlula igalelo le-methylene blue. Ukuvavanya ngokuphindaphindiweyo nokuxela iziphumo ezikhethiweyo kunokuwugqwetha ngakumbi umfanekiso. Ezo ngxelo zinokuvelisa imibuzo yophando, kodwa azinakubala iminyaka ezuzwayo.
Oko kuthethwa koku kwisigqibo ngobomi obude
Iziphumo ezikhoyo zixhasa uphando olungakumbi, hayi isixa okanye ishedyuli esele imiselwe yokusetyenziswa ngenjongo yobomi obude. Iminyaka yokusetyenziswa ngenjongo yokuthintela ingafuna ubungqina ngomonakalo oqokelelekayo kunye neenzuzo. Ileyibhile yangoku yemveliso etofwayo ichaza ukusebenzisana okuyingozi okuchaphazela inkqubo yeserotonin nokungavumeleki kokusetyenziswa xa kukho ukunqongophala kwe-G6PD ngenxa yomngcipheko wokutshatyalaliswa kweeseli ezibomvu zegazi. Ayiqinisekisi ukusetyenziswa ngomlomo ixesha elide ngenjongo yokujongana nokuguga.
Ngaphambi kokucinga ngokuyisebenzisa ngokwakho, hlola iziphumo ebezingalindelekanga neemeko apho ingafanele kusetyenziswa khona uze uxoxe nengcali yezonyango ngemveliso ethile nangoluhlu lwamayeza owasebenzisayo. Ukuhlola ibango lobomi obude, funa inkcazelo yento ephilayo efundiweyo, indlela yokunikwa, ixesha lokuchanabeka, into esetyenziswe ukuthelekisa, nesiphumo esilinganiswe ngokwenene. Ukuba isiphumo esilinganisiweyo kukukhula kweeseli okanye amanqaku ovavanyo, ibango kufuneka lihlale limalunga nokukhula kweeseli okanye loo manqaku ovavanyo.