▎ 5-Amino-1MQ Bincike
Menene asalin bincike na 5-Amino-1MQ?
A cikin yanayin ci gaba na lafiyar lafiyar jiki da bincike na tsawon rai, gano ingantattun hanyoyin magance rikice-rikice na rayuwa da jinkirta tsufa ya kasance babban mayar da hankali na kimiyya. Nicotinamide N-methyltransferase (NNMT) yana nuna babban aiki a cikin adipose nama da hanta. Ta hanyar methylating nicotinamide, yana rage jujjuyawar sa zuwa nicotinamide adenine dinucleotide (NAD⁺). NAD⁺ yana da mahimmanci ga ƙwayoyin basal metabolism, samar da makamashi, gyaran DNA, da hanyoyin sigina. Tsayawa mafi kyawun matakan sa yana da mahimmanci ga lafiyar salula da magance tsufa da rashin aiki na rayuwa. A cikin 2017, masu bincike a Jami'ar Texas sun fara binciken 5-Amino-1MQ yayin da suke neman hanyoyin hana NNMT. Ganin ƙaƙƙarfan haɗin kai na NNMT tare da kiba da nau'in ciwon sukari na 2, masu binciken sun yi hasashen cewa toshe NNMT na iya buɗe sabbin hanyoyin magance kiba da rikice-rikice na rayuwa. Wannan ya haifar da mahimman bayanan bincike na 5-Amino-1MQ.
Menene tsarin aiki don 5-Amino-1MQ?
Hana yaduwar kwayar cutar ciwon daji na mahaifa: 5MQ wani ƙananan ƙwayoyin cuta ne na nicotinamide N-methyltransferase (NNMT) wanda ke nuna tasirin antiproliferative a kan layin HeLa epithelial cervical carcinoma cell cell, tare da wannan sakamako ya zama maida hankali-da kuma dogara lokaci. NNMT shine enzyme na rayuwa wanda ke hade da ci gaban ƙari da metastasis. Ta hanyar hana NNMT, 5MQ mai yiwuwa ya rushe jerin hanyoyin rayuwa na ciki da ke da alaƙa da haɓakar ƙari. Misali, 5MQ na iya tsoma baki tare da hanyoyin sigina masu alaƙa da nicotinamide. Rashin daidaituwa a cikin metabolism na nicotinamide na iya kara yin tasiri ga metabolism na makamashin salula, gyaran DNA, da sauran matakai, ta yadda zai hana yaduwar kwayar cutar kansa. A cikin gwaje-gwajen, yayin da ƙaddamarwar 5MQ ya karu da kuma tsawaita lokacin jiyya, yaduwar kwayar halitta ta HeLa ta nuna ci gaba da bayyana hanawa. A lokaci guda, sauye-sauyen ilimin halittar jiki ciki har da raguwar tantanin halitta, asarar mannewar intercellular, da jikin apoptotic an lura da su, yana nuna cewa 5MQ yana haifar da apoptosis, don haka yana hana yaduwar kwayar halitta [1].
Tsarin Tsarin Halitta masu alaƙa da Bayyanar Protein: Bayan jiyya na 5MQ na ƙwayoyin HeLa, matakan mRNA na ZEB1, SIRT1, da CD16 sun ƙaru, yayin da matakan TWIST da SERPIN1 mRNA suka ragu. A lokaci guda, bayyanar cututtukan oncogenic phospho-Akt da SIRT1 sun ragu. Wadannan kwayoyin halitta da sunadaran suna taka muhimmiyar rawa a cikin tumorigenesis da ci gaba. Misali, TWIST da SERPIN1 yawanci suna da alaƙa da mamayewar ƙari da metastasis. Ta hanyar rage furcinsu, 5MQ na iya murkushe iyawar ɓangarorin ɓangarorin HeLa. Kodayake matakan mRNA na ZEB1 da SIRT1 sun karu, maganganun furotin na oncogenic SIRT1 ya ragu. Wannan na iya faruwa saboda 5MQ yana rinjayar ka'idojin rubutu bayan rubuce-rubuce, yana hana aikin furotin SIRT1 kuma ta haka yana rinjayar yaduwar kwayar halitta da rayuwa. Phosphorylated Akt yana taka muhimmiyar rawa a cikin rayuwar sel, yaduwa, da tsarin rayuwa. Ragewar 5MQ a cikin maganganunsa na iya hana yaduwar kwayar cutar kansa da rayuwa ta hanyar toshe hanyoyin sigina masu alaƙa [1].
Menene aikace-aikacen 5-Amino-1MQ?
A cikin binciken kiwon lafiya na rayuwa, ainihin aikinsa shine dawo da ma'auni na rayuwa ta hanyar hana NNMT. NNMT yana cinye nicotinamide (mafificin NAD⁺) kuma yana tasiri metabolism mai ba da gudummawar methyl, yayin da 5-Amino-1MQ ya toshe wannan tsari: a hannu ɗaya, yana rage yawan amfani da nicotinamide methylation a cikin adipocytes, haɓaka matakan NAD⁺ na intracellular don kunna NAD⁺-dogara na tsawon rai aiki-da kuma inganta ayyukan SIRT1. yana inganta lipolysis, yana hana lipogenesis, yana taimakawa wajen daidaita makamashin makamashi a cikin nama mai adipose, kuma yana rage yawan kitsen mai. Har ila yau, yana rage juriya na insulin da aka saba gani a cikin rikice-rikice na rayuwa ta hanyar inganta yanayin siginar insulin, yayin da mai yiwuwa a kaikaice yana daidaita gluconeogenesis na hanta don taimakawa wajen kiyaye matakan glucose na jini. Bugu da ƙari, yuwuwar tasirin sa akan microbiota yana ƙarƙashin bincike, tare da hasashe cewa yana iya tallafawa gabaɗayan homeostasis na rayuwa a kaikaice ta hanyar daidaita ayyukan ƙwayoyin cuta na ƙwayoyin cuta (misali, rage haɓakar haɓakar ƙwayoyin cuta).
A cikin binciken ciwon daji, aikace-aikacen sa yana mai da hankali kan niyya ga 'lalacewar ƙwayar cuta' na ƙwayoyin ƙari. Don ci gaba da yaduwa cikin sauri, ƙwayoyin ƙwayar cuta sukan dogara da hanyoyin rayuwa marasa aiki (kamar tasirin Warburg), kuma NNMT yana bayyana sosai a cikin wasu ƙwayoyin ƙwayar cuta, suna tallafawa metabolism. Ta hanyar hana NNMT, 5-Amino-1MQ yana rushe ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta ta hanyoyi biyu: Na farko, yana rage matakan NAD⁺ na ciki na ciki, yana lalata samar da makamashi, yana haifar da rashin isasshen makamashi da abubuwan da ake bukata na biosynthetic don haɓakawa; Na biyu, yana ɓata amfani da masu ba da gudummawar methyl, yana rushe tsarin tsarin tsarin epigenetic kamar DNA methylation a cikin ƙwayoyin ƙari, ta haka yana hana maganganun jinsin da ke da alaƙa da haɓakawa da metastasis. Bugu da ƙari, yana iya hana haɓakar ƙwayar cuta a kaikaice da yaduwa ta hanyar daidaita abubuwan da ke haifar da rayuwa a cikin microenvironment na ƙari, yana ba da tushe don bincika dabarun shiga tsakani na ƙari.
A matsayin kayan aikin bincike na asali, yana aiki azaman hanya mai mahimmanci don tantance ayyukan ilimin lissafin jiki na NNMT. Masu bincike za su iya toshe ayyukan NNMT daidai ta amfani da 5-Amino-1MQ a cikin salon salula ko ƙirar dabba don lura da canje-canje na gaba a cikin alamun rayuwa. Misali, a cikin gwaje-gwajen wayar salula, saka idanu kan tattarawar NAD⁺, matakan masu ba da gudummawa na methyl, da ayyukan enzymes da ke cikin haɗakar fatty acid na iya fayyace takamaiman rawar NNMT a cikin metabolism na salula. A cikin ƙirar dabba, haɗe tare da takamaiman samfurin samfurin nama, yana ba da damar bincika takamaiman ayyuka na nama na NNMT-kamar tasirin sa akan metabolism na hanta yayin tsufa ko tsarin samar da kuzari a cikin ƙwayoyin cuta. Bugu da ƙari, ƙaddamar da martani daban-daban a cikin layin salula (misali, sel na yau da kullun suna nuna ƙarancin hankali tare da fayyace martani a cikin ƙwayoyin cuta marasa ƙarfi ko ƙari) na iya taimakawa wajen tantance takamaiman hanyoyin rayuwa ta salon salula, jagorantar bincike da aka yi niyya na gaba.
A cikin sassan lafiyar tsoka da fahimi, aikace-aikacen sa ya dogara ne akan alaƙar 'makamashi metabolism - aikin salula'. A cikin binciken lafiyar tsoka, gyaran tsoka yana dogara ne akan kunnawa da haɓakar ƙwayoyin tauraron dan adam, tsarin da ke buƙatar isasshen makamashi. -5-Amino-1MQ yana haɓaka kunnawar tauraron dan adam ta hanyar kiyaye matakan NAD⁺ na ciki a cikin ƙwayoyin tsoka. A lokaci guda, yana haɓaka aikin mitochondrial don haɓaka ƙarfin kuzarin tsoka da haɓaka haɓakar haɓakar ƙwayar tsoka, yana rage damuwa na dawowa bayan rauni na tsoka. Hakanan yana iya rage danniya mai iskar oxygen a cikin nama na tsoka, yana kare sel daga lalacewa ta hanyar wuce gona da iri na rayuwa. A cikin bincike na fahimi, jijiyoyi na kwakwalwa suna nuna buƙatun makamashi mai yawa, kuma raguwar matakan NAD⁺ yana da alaƙa da raguwar ayyukan jijiyoyi. 5-Amino-1MQ yana adana samar da NAD⁺ neuronal ta hanyar hana NNMT, don haka kiyaye aikin mitochondrial da rage kumburin neuroinflammation. Hakanan yana iya rinjayar metabolism na neurotransmitter (ta hanyar NAD⁺-enzymes masu dogaro da ke cikin haɗin gwiwar neurotransmitter) don tallafawa ayyukan neuronal masu alaƙa da fahimi (misali, aikin salula a cikin koyo / yankunan ƙwaƙwalwar ajiya kamar hippocampus), yana ba da ra'ayi na sabon salo don bincike na kiyaye aikin fahimi.
Kammalawa
A matsayin ƙayyadaddun mai hana nicotinamide N-methyltransferase (NNMT), 5-Amino-1MQ yana nuna ƙimar mahimmanci a cikin yankuna da yawa ta hanyar ƙaddamar da hanyoyin NNMT da aka tsara na rayuwa. Yana iya inganta kiba da juriya na insulin ta hanyar kiyaye matakan NAD⁺, inganta aikin mitochondrial, da dawo da ma'auni na rayuwa. Har ila yau, yana kaiwa hari ga raunin da ya faru a cikin ƙwayoyin tumor, yana tarwatsa samar da makamashin su da ka'idojin epigenetic don hana ci gaban ƙari. Bugu da ƙari kuma, yana aiki azaman kayan aikin bincike don bayyana aikin NNMT yayin da yake nuna yuwuwar rawar da ake takawa a cikin gyaran tsoka da kulawar fahimi, samar da mahimman kwatance don nazarin shiga tsakani a cikin cututtukan rayuwa, ciwon daji, da yanayi masu alaƙa.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Akar s wani mai bincike ne wanda aikinsa ya mayar da hankali kan hanyoyin kwayoyin halitta da hanyoyin warkewa. Ya ba da gudummawa ga binciken da ke bincikar tasirin enzymes da ƙananan ƙwayoyin ƙwayoyin cuta a cikin daidaita ƙwayar salula. Bincikensa ya jaddada mahimmancin ƙaddamar da hanyoyi na rayuwa, irin su nicotinamide N-methyltransferase, don gano sababbin dabarun ilimin halitta. An jera Akar s a cikin ma'anar ambato [2].
