epigenetic priming

epigenetic priming (janyu priming anie kooda pilustaaru) anedi oka kanam yokka epigenomecu maarpu, dheeni dwara oka kanam lopala nirdishta chromatin domainlu closed state nundi open statega maarchabadataayi, saadhaaranamgaa bahya jeeva trigger ledhaa maargam phalitamgaa, transcription karakalu ledhaa itara savarana yantraamgaala dwara dna accessnu anumatistundi. dna yokka oka nirdishta praantaaniki epigenetic priming yokka charya itara janyu niyantrana yantraamgaalu kana jeevitamlo taruvaata dnapy elaa panichestayo nirdesistundi. epigenetic priming pradhanamgaa neurosines mariyu cancer parisoedhanaloo parisoedhimchabadimdi, endukante idhi varusaga neuronlalo ghnaapakasakti erpadatamlo mariyu cancer chikitsalo tumour-suppressor janyu kriyaaseelataloo keelaka paatra pooshistundani kanugonabadindi.
yantraangam.
epigenetic priming anedi aushadham ledhaa paryaavarana maarpulu vanti uddeepanala dwara prerepinchabadina gupta epigenetic sthithini suuchistumdi. epigenetically primed state chromatin vadulugaa undatam dwara vargeekarinchabadutundi, idhi chromatin sthithini heterochromatin (kathinamgaa bandhinchabadina mariyu cherukolenidi) nundi eukromatin (vadulugaa bandhinchabadina mariyu puurtigaa andubaatulo undedi) kii marchadam, idhi sulabhamgaa cherukovadam mariyu transcription kaarakaala bandham phalitamgaa konni janyuvula transcriptionku daariteestundi. trigger signal vividha epigenetic mechanisms dwara prabhaavitamavutundi, veetilo atyanta pramukhamainavi histone acetylation mariyu histone methylation. histone dactylase (hcdc) vaeriyantlu vanti histone maarpulalo palgone epigenetic agentlu chaalaa varaku lakshyamgaa laevu, antey chromatin yokka vaduladam mariyu biginchadam kanamlo nirdishtamgaa undadu. anduvalla, epigenetic priming mariyu phalitamgaa janyu transcription kanamantataa jarugutundi mariyu aneka rakaala chromatin pradaesaalanu prabhaavitam chestundi.
histone acetylation mariyu methylation vanti chromatin punarnirmaana prakriyalu tiragagalavu, mariyu epigenetic priming phalitamgaa eukromatin saitlu chivariki histone decitylase vanti tiragagala agentla dwara tirigi heterochromatinga maarchabadataayi. anduvalla, chromatin terichi undataaniki kanamlooni eee reversal agentlanu nirodhinchadam dwara primingnu krutrimamgaa niyantrinchavacchu. eee vidhanalalo, baga adhyayanam cheyabadinadi hcdc nirodham.
hetch. dii. yea. sii. nirodham.
epigenome plaastisitiini nirvahinchadaaniki, vividha epigenetic gurtulanu jodinche (raitars) mariyu tolaginche (eragers) enjaimlu avasaram. paie epigenetic priming modal chitramlo histone acetylation udaaharanagaa, eee rachayitalu mariyu eragerla madhya paraspara charya undhi, idhi janyuvu bahya ledhaa antargata uddeepanalaku pratispandinchadaaniki veelu kalpistundi. acetylation vishayamlo, histone acetyl transferes histonelaku acetyl samuuhaalanu jodistundi mariyu histone desetylase (hcdc) vaatini tolagistundi. rendoo oka nirdishta samayamlo oka kanamlo untaayi, antey chromatin yokka acetylated (open) praantaanni closed roopaaniki tirigi maarchavacchu. hcdc nirodham anedi chromatin open tuu closed transitionnu nishedhinchadam dwara open state loe undela chestundi, idhi shaashwata janyu vyakteekarana mariyu itara epigenetic kaaryakalaapaalaku daariteestundi.
cancer.
kaniti-anachivese janyuvulapai (tsg) epigenetic maarpulu carcinogenesis yokka driverluga kanugonabadinappudu epigenetic priming modata cancer parisoedhanaloo vivarinchabadindi. epigenetic maarpulu (udhaa.zii. dna methylation) phalitamgaa kaniti erpadataaniki oka saadhaarana maargamgaa tsg nishkriyam avutundi. cancerlo saadhaarana dna utparivartanalaku viruddhamgaa, methylation tirigi cheyavachu, ayithe hypomethylating agentlanu dnnu access cheyadaaniki mariyu methylation nivaarinchadaaniki chromatin taginantagaa terichi untundi. anduvalla, decitabine vanti hypomethylating chemotherapeuticsku tumerogenic kanaalanu sunnitamgaa cheyadaaniki primingnu 'prii-treatment' gaa parisoedhimchaaru. aneka rakaala cancerlu (udhaa.zii. gastric) asaadhaaranamaina epigenetic maarpulaku prasiddhi chendaayi, mukhyamgaa dna methylationlo. chikitsa dwara sulabhamgaa maarchaleni dna utparivartanalaku viruddhamgaa, eee asaadhaarana epigenetic maarpulu tirigi marchagala chikitsa marganni anumatistaayi.
epigenetic agentlu asadhaaranamgaa nissabdamaina janyuvula vyakteekarananu penchutaayani niroopinchabaddaayi (i.ii. 5-aza-cr chikitsa tarvaata elukala namoonaalalo namoonaalalo, tnf, picard, fas). anduvalla, cancer-prerita kana panicheyakapovadaanni adhigaminchadaaniki sahaayapadutundi. adanamgaa, epigenetic priming cancer aushadhaala cytotoxicityni penchutundani choopabadindi (i.ii. (i.ii mariyu sii. dii. dii. pii), oopiritittulu mariyu andaasaya cancerlo aasaajanaka phalitaalanu chuuputoemdi. vaati niroopitamaina prabhaavaseelata kaaranamgaa, fda 5-ajacitidine, romidepsin mariyu itara dmnt inhibitarlanu aamodinchindi (antey.ii. 5-ajacitidine, hydrologyne, 5-aja-2 '-dioxycytidine) mariyu hcdc inhibitors (antey.ii. clinical upayogam kosam romidepsin, belinostat, panobinostat). 
clinical trials.
cancer chikitsalo mundastu chikitsagaa epigenetic chikitsa yokka bhadrata mariyu prabhavanni anchanaa vaeyadaaniki aneka clinical trials jarigaayi. 5-ajacitidine (dnmt inhibitor) mariyu romidepsin (hcdc inhibitor) vanti epigenetic agentla preclinical vadakam tadupari chikitsa kosam cancer kanaalanu sunnitamgaa chestundi. nirvahinchina clinical trials yokka konni udaaharanalu krinda ivvabaddaayi. 
colorectal cancer.
pembrolizumab paripalanaku mundu 5-ajacitidine (5-aja) mariyu romidepsin thoo epigenetic chikitsanu 2016-2018 nundi clinical triallo bhadrata kosam pareekshinchaaru. 40-69 samvatsaraala madhya vayassu gala 24 mandhi rogulalo aushadha nirvahana (5-aja, romidepsin, 5-aja + romidepsin) 14 rojula paatu anusarinchabadindi. samoohaalalo dushprabhavalalo atisaaram, vikaram mariyu alasata unnaayi. antekakunda, aakali lekapovadam, raktaheenata mariyu thrombocytopenia anevi roogi andukunna aushadha kalayika nundi swatantramgaa undevi. eee adhyayanam taruvaata, 5-ajaa mariyu romidepsin thoo epigenetic agent 'pretherapy' taruvaata pembrolizumab chikitsa saadhyamayyedigaa mariyu rogulaku mottam surakshitamainadigaa pariganinchabadindi.
gastric carcinomas.
gastric cancer epigenetic apperrations dwara ekkuvagaa prabhaavitamavutundi. point mutationla kante dna methylation maarpulu gastric cancerpy ekkuva prabhavanni chuuputaayani vislaeshanhaloo telindi. gastric cancer 5-ajaapai epirubisin, oxalyplatin mariyu capsitabine kalayikatho modati dasha adhyayanam vijayavantamaindi. demethylating lokilo epigenetic jokyam phalavantamainadi (i.ii. cdkn2a, Esr1, hpp1, mgmt, timp3) gastric carcinomalo asadhaaranamgaa methylated.
teevramaina milogenous leukemia.
modati dasha adhyayanam teevramaina milogenous leukemia (ml) unna rogulalo decitabinetho epigenetic priming yokka saadhyatanu anveshinchindi, taruvaata cytarabin mariyu downorubisin chikitsa jarigindi. rogulaku roganirodhaka chikitsaku rendu vaaraala mundu 1 ganta infusion (group eah) ledhaa 3 ledhaa 7 rojula (group bii) nirantara infusiontho chikitsa andinchaaru. group bii chikitsa tarvaata group eah kante adhika sthaayi hypomethylation choopinchindi, conny epigenetic agent dwara vishapuuritam choopinchaledu. chivaraku, etuvanti mukhyamaina dushprabhaavaalu kanipinchaledu.
aaml roganirdhaarana unna vruddha rogulaku paelavamaina rooga niruupana, puurti upasamanam yokka takkuva raetlu mariyu mottam manugada marinta digajaradam untaayi. aaml unna vruddha rogulalo decitabine dwara epigenetic priming yokka samarthatha mariyu bhadratanu anchanaa vaestuu 2va dasha adhyayanam nirvahinchabadindi. nirvahinchabadindi, intensive chemotherapyki abhyardhulu kaani 46 mandhi rogulu adhyayanamlo namodu chesukunnaru. chikitsalo decitabine yokka nirantara IV paripalana, taruvaata 5 rojula cyterabine immunotherapy unnaayi. 15 rojula emuka majja biopsylo vyaadhi yokka aadharalu kanugonabadithe rogulu rendava chakramtho konasagaru, lekapothe, vaaru decitabine nirvahanato munduku sagaru. decitabine thoo mundastu chikitsa taruvaata cytarabine anedi aaml thoo unna vruddha rogulalo adhika sankhyalo puurti upasamanaalanu (70 saatam) prothsahinchindani adhyayanam choopinchindi.
neurosines.
epigenetic maarpulu, mukhyamgaa epigenetic priming chesevi, neuronla lopala memory encodingku praathamikamgaa baadhyata vahistaayani nammutaaru. eee aalochanaku vividha aadharalu maddatu istunnaayi. modata, ghnaapakasakti erpade samayamlo protein samslaeshanha nirodhinchabadinappatiki, ghnaapakaalu taruvaata tirigi pondavacchu. idhi, synaps ksheenata tarvaata deerghakaalika ghnaapakasaktini punaruddharinchavachani kanugonna daanitoe paatu, synaptic nirmaanam (ghnaapakasakti erpade samayamlo protein samslaeshanha avasaram) anedi kanamlo encrom encodingku praathamika muulam kaadani suuchistumdi. inca, elukalalo ghnaapakasakti erpadataaniki saraina histone acetranspherase function avasaramani mariyu neuronlalo hcdc nirodham abhyasa pravartananu mariyu deerghakaalika ghnaapakasaktini meruguparustundani kanugonabadindi. oka vivarana emitante, ghnaapakasakti-sambandhita naadii kaaryakalaapaalato kalisinappudu, hcdc inhibitorlu (hdaci) chromatin terichi undataaniki mariyu synapsesnu punarnirminche janyuvula transcription penchadaaniki anumatistaayi, phalitamgaa plasticity perugutundi mariyu merugaina ghnaapakasakti erpadutundi. eee pariseelanala phalitamgaa, epigenetic priming anedi ghnaapakasakti erpadataaniki prarambha dasha anie pratipaadinchabadindi.
deerghakaalika ghnaapakasakti yokka vividha roopaalu vividha rakaala histone acetylationlatho mudipadi unnayani kanugonabadindi, udaaharanaku udaaharanaku verses verses yokka acetylation. idhi neuronlalo epigenetic priming, idhi ververu memory profile vyakteekaranalaku daariteestundani suuchistumdi, vividha histone acetyl transferrages dwara encode cheyabadavachhu. anduvalla, chromatin vippinche yantraamgaalu vaati lakshyamlo nirdishtamgaa laenappatikee, evi sakriyam cheyabadatayo batti nirdishtatanu kaligi untaayi. idhe vidhamaina siralo, histone acetyl transferesla rakalu vanti vividha priming agentla charya, neuron chromatinpy stocking prabhavanni srushtinchadaaniki militam cheyavachani nammutaaru, phalitamgaa anubandha janyuvula vyakteekarana gananeeyamgaa perugutundi.
metabolic syndrome.
prarambha abhivruddhi samayamlo talli poeshanha mariyu shareera kuurpu vanti paryaavarana karakalu santaanam yokka jeevakriya samalakshanaanni prabhaavitam cheyagalavani epidemiological mariyu prayogaatmaka adhyayanalu choopinchaayi. epigenetic priming anedi janyu vyakteekaranalo nirantara maarpulaku madhyavartitvam vahistundani bhaavistaaru, idhi chivariki jeevakriya syndromeku daariteestundi. sambhaavyamgaa, eee prerita jeevakriya antaraayaalu takkuva vanarula vaataavaranamloo abhivruddhi chendutunna santaanaaniki prayojanam chekuurustaayi, tadwara taruvaata jeevitamlo vijayam saadhinchavachchu. agouti eluka santaanam yokka aarogyampai prarambha paryaavarana bahirgatam yokka paina perkonna prabhavam yokka vaividhyaanni udaharistundi.

