PRODUCTION AND Application OF ANGIOSTATINS FOR THE TREATMENT OF OCULAR NEOVASCULAR DESEASES
Biotechnologia Acta ; 14(one):5-24, 2021.
Artigo em Inglês
| ProQuest Key | ID: covidwho-1136887
ABSTRACT
Angiostatins comprise a group of kringle-containing proteolytically-derived fragments of plasminogen/plasmin, which human activity as potent inhibitory mediators of endothelial cells proliferation and migration. Angiostatins are involved in modulation of vessel growth in healthy tissues and various pathological conditions associated with abnormal neovascularization. The aim of the present paper was to summarize bachelor information, including our own experimental data, on prospects of angiostatin application for treatment of ocular neovascular diseases (OND), focusing on retinal pathologies and corneal injury. In particular, literature data on prospective and retrospective studies, clinical trials and animal models relating to the pathophysiology, investigation and management of OND are described. Special accent was fabricated on the laboratory approaches of production of dissimilar angiostatin isoforms, as well equally comparison of antiangiogenic capacities of native and recombinant angiostatin polypeptides. Several studies reported that angiostatins may completely abolish pathologic angiogenesis in diabetic proliferative retinopathy without affecting normal retinal vessel development and without exhibiting adverse side effects. Angiostatins take been tested as a tool for corneal antiangiogenesis target therapy in order to manage diverse ocular surface pathological weather condition induced by traumas, chemical burns, previous surgery, chronic contact lens clothing, autoimmune diseases, keratitis and viral infections (canker, COVID-19), corneal graft rejection, etc. Amid all known angiostatin species, isolated K5 plasminogen fragment was shown to display the most stiff inhibitory activeness against proliferation of endothelial cells via triggering multiple signaling pathways, which lead to prison cell death and resulting angiogenesis suppression. Application of adenoviral genetic construct encoding angiostatin K5 as a promising tool for OND handling illustrates a vivid case of upcoming revolution in local gene therapy. Farther comprehensive studies are necessary to elucidate the clinical potential and optimal regimes of angiostatin-based intervention modalities for treating ocular neovascularization.Alternate abstractÃÂýóÃ'‚Ã'ÂÃ'‚ðÃ'‚øýø Ã'ÂÃ'‚ðýþòûÃ'ÂÃ'‚Ã'Å' Ã'‚Ã'€Ã'Æ'ÿÃ'Æ' úÃ'€Ã¸Ã½Ã³Ã»(ÃÅ¡)-òü1Ã'ÂýøÃ'… ÿÃ'€Ã¾Ã'‚õþû1Ã'‚øÃ'‡Ã½Ã¸Ã'… Ã'„Ã'€Ã°Ã³Ã¼ÃµÃ½Ã'‚Ã'ˆ ÿûð÷üÃ'ˆÃ¾Ã³ÃµÃ½/ÿûð÷üÃ'ˆÃ'Æ', Ã'Âú1 Ã'„Ã'Æ'ýúÃ'‰Ã¾Ã½Ã'Æ'Ã'ŽÃ'‚Ã'Å' Ã'Âú ÿþÃ'‚Ã'Æ'öÃ'ˆ Ã'ˆÃ¿Ã±Ã'Æ'òðûÃ'Å'Ã'ˆ üõôÃ'‚Ã'‚þÃ'€Ã¸ ÿÃ'€Ã¾Ã»1Ã'„õÃ'€Ã°Ã'†Ã¿ Ã'‚ð Mirpauii õýôþÃ'‚õûÃ'ˆÃ½Ã¸Ã'… úûóóøý. Òþýø ñõÃ'€Ã'Æ'Ã'‚Ã'Å' Ã'Æ'Ã'‡Ã°Ã'ÂÃ'‚Ã'Å' Ã'Æ' üþôÃ'Æ'ûÃ'ŽÃ²Ã°Ã½Ã'ˆ Ã'€Ã¾Ã'ÂÃ'‚Ã'Æ' Ã'ÂÃ'Æ'ôøø Ã'Æ' Ã'‚úðýøýðÃ'… ÷ð ýþÃ'€Ã¼Ã¸ Ã'‚ð Ã'€Ã'ŽÃ½Ã¸Ã'… ÿðÃ'‚þûþóÃ'ˆÃ½Ã¸Ã'… Ã'ÂÃ'‚ðýÃ'ˆ, ðÃ'ÂþÃ'†Ã'ˆÃ¾Ã²Ã°Ã½Ã¸Ã'… ÷ ðñõÃ'€Ã°Ã½Ã'‚ýþÃ'Ž Ã½ÃµÃ¾Ã²Ã°Ã'ÂúÃ'Æ'ûÃ'ÂÃ'€Ã¸Ã·Ã°Ã'‰ÃµÃ'Ž. ÃÅ"õÃ'‚þÃ'Ž Ã'€Ã¾Ã±Ã¾Ã'‚ø ñÃ'Æ'ûþ Ã'Æ'÷ðóðûÃ'Å'ýõýýÃ' Ã½Ã°Ã'Âòýþ! İHÃ'„þÃ'€Ã¼Ã°Ã'†Ã¸, Ã'„þÃ'€Ã¼Ã°Ã'†Ã¸, òúûÃ'ŽÃ'‡Ã°Ã'ŽÃ'‡Ã¸ òûðÃ'ÂÃ'‚ õúÃ'ÂÿõÃ'€Ã¸Ã¼ÃµÃ½Ã'‚ðûÃ'Å'Hİ Ã´Ã°Ã'ˆ aBTopİB, Ã'‰Ã¾Ã´Ã¾ ÿõÃ'€Ã'ÂÿõúÃ'‚øò ÷ðÃ'ÂÃ'‚þÃ'ÂÃ'Æ'òðýýÃ' Ã°Ã½Ã³Ã'‚Ã'ÂÃ'‚ðÃ'‚øýÃ'Æ' ôûÃ' Ã»Ã'ˆÃ'Æ'òðýýÃ' Ã½ÃµÃ¾Ã²Ã°Ã'ÂúÃ'Æ'ûÃ'ÂÃ'€Ã½Ã¸Ã'… ÷ðÃ'…òþÃ'€Ã'ŽÃ²Ã°Ã½Ã'Å' þúð (ÃÂÃâ€"Þ). Ã“Ã¾Ã»à ¾Ã²Ã½Ã'Æ' Ã'Æ'òðóÃ'Æ' ÷þÃ'ÂõÃ'€ÃµÃ´Ã¶ÃµÃ½Ã¾ ýð ÿðÃ'‚þûþóÃ'ˆÃ'… cÃÂtkÃÂbkh Ã'‚ð Ã'Æ'Ã'ˆÃºÃ¾Ã´Ã¶ÃµÃ½Hİ porİBKH. Ãâ€"þúÃ'€ÃµÃ¼Ã°, þÿøÃ'Âðýþ ôðÃ'‚ Û1Ã'‚õÃ'€Ã°Ã'‚Ã'Æ'Ã'€Ã¸ Ã'ÂÃ'‚þÃ'Âþòýþ ÿõÃ'€Ã'ÂÿõúÃ'‚øòýøÃ'… Ã'‚ð Ã'€ÃµÃ'‚Ã'€Ã¾Ã'ÂÿõúÃ'‚øòýøÃ'… ôþÃ'ÂûÃ'‰Ã¶ÃµÃ½Ã'Å', úûÃ'ˆÃ'ˆÃ½Ã¸Ã'… òøÿÃ'€Ã¾Ã±Ã'Æ'òðýÃ'Å' i ÿðÃ'‚þÃ'„ÃÅ"þûþóÃ'ˆÃ½Ã¸Ã'… Ã'‚òðÃ'€Ã¸Ã½Ã½Ã¸Ã'… üþôõûõù, Ã'ÂÃ'‚òþÃ'€ÃµÃ½Ã¸Ã'… ôûÃ' Ã´Ã¾Ã'ÂûÃ'‰Ã¶ÃµÃ½Ã½Ã' Ã'‚ð ûÃ'ˆÃ'Æ'òðýýÃ' ÃÂÃâ€"Þ. ÞÃ'Âþñûøòøù ðúÃ'†ÃµÃ½Ã'‚ ñÃ'Æ'ûþ ÷Ã'€Ã¾Ã±Ã»ÃµÃ½Ã¾ ýð ûðñþÃ'€Ã°Ã'‚þÃ'€Ã½Ã¸Ã'… ÿÃ'‰Ã'…þôðÃ'… ôþ þÃ'‚Ã'€Ã¸Ã¼Ã°Ã½Ã½Ã' Ã'€Ã'ŽÃ½Ã¸Ã'… Ã'ŽÃ¾Ã'„þÃ'€Ã¼ ðýóÃ'‚Ã'ÂÃ'‚ðÃ'‚øýÃ'Æ', ð Ã'‚ðúþö ýð ÿþÃ'€Ã'ˆÃ½Ã'ÂýÃ'ˆ ðýÃ'‚øðýóÃ'‚óõýýøÃ'… òûðÃ'ÂÃ'‚øòþÃ'ÂÃ'‚õù ýðÃ'‚øòýøÃ'… Ã'‚ð Ã'€ÃµÃºÃ¾Ã¼Ã±Ã'ˆÃ°Ã½Ã'‚ýøÃ'… ÿþû1ÿõÿÃ'‚øôÃ'ˆ-ðýóÃ'‚Ã'ÂÃ'‚ðÃ'‚øÃ'ˆÃ². ôÃ'ˆ-ðýóÃ'‚Ã'ÂÃ'‚ðÃ'‚øÃ'ˆÃ². àõ÷Ã'Æ'ûÃ'Å'Ã'‚ðÃ'‚ø cepii ôþÃ'ÂûÃ'‰Ã¶ÃµÃ½Ã'Å' Ã'Âò1ôÃ'‡Ã°Ã'‚Ã'Å', Ã'‰Ã¾Ã°Ã½Ã³Ã'‚Ã'ÂÃ'‚ðÃ' øýø üþöÃ'Æ'Ã'‚Ã'Å' ÿþòý1Ã'ÂÃ'‚Ã'Ž Ã¿Ã'€Ã¸Ã³Ã'ˆÃ'‡Ã'Æ'òðÃ'‚ø ÿðÃ'‚þûþÿÃ'‡Ã½Ã¸Ã¹ ðýÿþóõýõ÷ ÷ð Ãâ€1ðñõTH4HOÃŽ TH4HOÃŽ ÿÃ'€Ã¾Ã»1Ã'„õÃ'€Ã°Ã'‚øòýþ1 Ã'€ÃµÃ'‚øýþÿðÃ'‚ø, ýõ òÿûøòðÃ'ŽÃ'‡Ã¸ ýð ýþÃ'€Ã¼Ã°Ã»Ã'Å'ýøù Ã'€Ã¾Ã·Ã²Ã¸Ã'‚þú Ã'ÂÃ'Æ'ôøý cÃÂtkÃÂbkh Ã'‚ð ýõ òøÃ'ÂòûÃ'ÂÃ'ŽÃ'‡Ã¸ ýõÃ'ÂÿÃ'€Ã¸Ã'ÂÃ'‚ûøòøÃ'… ÿþñÃ'ˆÃ½Ã¸Ã'… õÃ'„õúTİB. ÃÂýÿþÃ'ÂÃ'‚ðÃ'‚øýø òøÿÃ'€Ã¾Ã±Ã¾Ã²Ã'Æ'Ã'ŽÃ'‚Ã'Å' Ã'Âú Ã'ˆÃ'ÂÃ'‚Ã'€Ã'Æ'üõýÃ'‚ ôûÃ' Ã'‚ðÃ'€Ã³ÃµÃ'‚ýþ! ðýÃ'‚øðýÿþóõýýþ! Tepami Ã'€Ã¾Ã³Ã'ˆÃºÃ¸ ÷ üõÃ'‚þÃ'Ž Ã»Ã'ˆÃ'Æ'òðýýÃ' Ã'€Ã'ŽÃ½Ã¾Ã¼Ã°Ã½Ã³Ã³Ã½Ã¸Ã'… ÿðÃ'‚þûþÿÃ'‡Ã½Ã¸Ã'… Ã'ÂÃ'‚ðÃ'ˆÃ² þÃ'‡Ã½Ã¾! ÿþòõÃ'€Ã'…Ã'ˆ, Ã'ÂÿÃ'€Ã¸Ã'‡Ã¸Ã½ÃµÃ½Ã¸Ã'… Ã'‚Ã'€Ã°Ã²Ã¼Ã°Ã¼Ã¸, XÃÂMÃÂ4HHMH þÿÃ'ˆÃ°Ã¼Ã¸, ÿþÿõÃ'€ÃµÃ´Ã½Ã'ˆÃ¸ þÿõÃ'€Ã°Ã'‚øòýøüø òÃ'‚Ã'€Ã'Æ'Ã'‡Ã°Ã½Ã½Ã'Âüø, ßÞáâèÃÂÃËœÃÅ" ÃÂÞáèÃÂïÃÅ" úþýÃ'‚ðúÃ'‚ýøÃ'… ûÃ'ˆÃ·, ðòÃ'‚þÃ'ˆÃ'Æ'ýýøüø ÷ðÃ'…òþÃ'€Ã'ŽÃ²Ã°Ã½Ã½Ã'Âüø, úõÃ'€Ã°Ã'‚øÃ'‚ðüø Ã'‚ð òÃ'„Ã'Æ'Ã'Âýøüø Ã'ˆÃ'„õúÃ'†Ã'ˆÃ¼Ã¸ (óõÃ'€Ã¿ÃµÃ'Â, COVID-19), òÃ'‰Ã'‚þÃ'€Ã³Ã½ÃµÃ½Ã½Ã'Âü Ã'‚Ã'€Ã°Ã½Ã'ÂÿûðýÃ'‚ðÃ'‚ð Ã'€Ã¾rİBKH Ã'‚þÃ'‰Ã¾. áõÃ'€ÃµÃ´ ycix òÃ'‰Ã¾Ã¼Ã¸Ã'… 1÷þÃ'„þÃ'€Ã¼ ðýÿþÃ'ÂÃ'‚ðÃ'‚øÃ'ˆÃ² Ã'ŽÃ¾Ã»Ã'Å'þòðýøù Ã'„Ã'€Ã°Ã³Ã¼ÃµÃ½Ã'‚ ÿûð÷üÃ'ˆÃ¾Ã³ÃµÃ½ 'Æ' ÃÅ¡five òøÃ'ÂòûÃ'Âõ ýðùÿþÃ'‚Ã'Æ'öÃ'ˆÃ'ˆÃ'Æ' Ã'ˆÃ¿Ã±Ã'Æ'òðûÃ'Å'ýÃ'Æ' ðúÃ'‚øòHİCTB Ã'ÂÃ'‚þÃ'Âþòýþ ÿÃ'€Ã¾Ã»1Ã'„õÃ'€Ã°Ã'†Ã¸ õýôþÃ'‚õûÃ'‚ûÃ'Å'ýøÃ'… úû1Ã'‚øý, ÿÃ'€Ã¸Ã³Ã½Ã'ˆÃ'Æ'Ã'ŽÃ'‡Ã¸ ĪĪ Ã'‡ÃµÃ'€ÃµÃ· ðúÃ'‚øòðÃ'‰Ã'Ž Ã¼Ã½Ã¾Ãâ€"ÃÂÃÂÃÂÃÂÃÂ¥ áÃÂÓÃÂðÛìÃÂÃÂÃÂ¥ èÛïÃÂ¥1Ã’, Ã'‰Ã¾ ÿÃ'€Ã¸Ã·Ã²Ã¾Ã´Ã'ÂÃ'‚Ã'Å' ôþ ÷ðóøñõûane úûóóøý Ã'‚ð cynpeciàðýóÃ'ˆÃ³ÃµÃ½ÃµÃ·Ã'Æ'. Ãâ€"ðÃ'ÂÃ'‚þÃ'ÂÃ'Æ'òðýýÃ' Ã°Ã´ÃµÃ½Ã¾Ã²Ã'„Ã'Æ'Ã'Âýþ! óõýõÃ'‚øÃ'‡Ã½Ã¾! úþýÃ'ÂÃ'‚Ã'€Ã'Æ'úÃ'†Ã¸, Ã'‰Ã¾ úþôÃ'Æ'õ ðýóÃ'ˆÃ'ÂÃ'‚ðÃ'‚øý ÃÅ¡5, Ã'Âú ÿõÃ'€Ã'ÂÿõúÃ'‚øòýþóþ ÷ðÃ'ÂþñÃ'Æ' úþÃ'€ÃµÃºÃ'†Ã¸ ÃÂÃâ€"Þ õ Ã'ÂÃ'ÂúÃ'€Ã°Ã²Ã¸Ã¼ ÿÃ'€Ã¸ÃºÃ»Ã°Ã´Ã¾Ã¼ Ã'€ÃµÃ²Ã¾Ã»Ã'ŽÃ'†Ã'ˆÃ½Ã¾Ã³Ã¾ Ã'ˆÃ´Ã'…þôÃ'Æ' ò Ã'‚ðÃ'€Ã³ÃµÃ'‚ýÃ'ˆ óõýýÃ'ˆ Tepami. Òòðöðõüþ ÷ð ôþÃ'‰Ã»Ã'Å'ýõ ÿÃ'€Ã¾Ã²ÃµÃ´ÃµÃ½Ã¸Ã' Ã¿Ã¾Ã´Ã°Ã»Ã'Å'Ã'ˆÃ¸Ã'… úþüÿûõúÃ'ÂýøÃ'… ôþÃ'ÂûÃ'‰Ã¶ÃµÃ½Ã'Å' ôûÃ' Ã·'Ã'ÂÃ'ÂÃ'Æ'òðýýÃ' ÃºÃ»Ã'ˆÃ'ˆÃ½Ã¾Ã³Ã¾ ÿþÃ'‚õýÃ'‰Ã°Ã»Ã'Æ' Ã'‚ð þÿÃ'‚øüðûÃ'Å'ýøÃ'… Ã'€ÃµÃ¶Ã¸MİB òøúþÃ'€Ã¸Ã'ÂÃ'‚ðýýÃ' Ã·Ã°Ã'ÂþñÃ'ˆ ýð ochobàðýóÃ'ŽÃ'ÂÃ'‚ðÃ'‚øýÃ'Æ' ôûÃ' Ã»Ã'ˆÃ'Æ'òðýýÃ' Ã½ÃµÃ¾Ã²Ã°Ã'ÂúÃ'Æ'ûÃ'ÂÃ'€Ã½Ã¸Ã'… ÿðÃ'‚þûþóÃ'ˆ þúð.Alternate abstractÃÂýóøþÃ'ÂÃ'‚ðÃ'‚øýÃ'‹ Ã'ÂþÃ'ÂÃ'‚ðòûÃ'ÂÃ'ŽÃ'‚ óÃ'€Ã'Æ'ÿÿÃ'Æ' úÃ'€Ã¸Ã½Ã³Ã» (ÃÅ¡)-Ã'Âþ ôõÃ'€Ã¶Ã°Ã'‰Ã¸Ã'… ÿÃ'€Ã¾Ã'‚õþûøÃ'‚øÃ'‡ÃµÃ'ÂúøÃ'… Ã'„Ã'€Ã°Ã³Ã¼ÃµÃ½Ã'‚þò ÿûð÷üøýþóõý/ÿûð÷üøýð, úþÃ'‚þÃ'€Ã'‹Ãµ Ã'„Ã'Æ'ýúÃ'†Ã¸Ã¾Ã½Ã¸Ã'€Ã'Æ'Ã'ŽÃ'‚ úðú üþÃ'‰Ã½Ã'‹Ãµ øýóøñøÃ'€Ã'Æ'Ã'ŽÃ'‰Ã¸Ãµ üõôøðÃ'‚þÃ'€Ã'‹ ÿÃ'€Ã¾Ã»Ã¸Ã'„õÃ'€Ã°Ã'†Ã¸Ã¸ ø üøóÃ'€Ã°Ã'†Ã¸Ã¸ Ã'ÂýôþÃ'‚õûøðûÃ'Å'ýÃ'‹Ã'… úûõÃ'‚þú. ÃÂýóøþÃ'ÂÃ'‚ðÃ'‚øýÃ'‹ Ã'Æ'Ã'‡Ã°Ã'ÂÃ'‚òÃ'Æ'Ã'ŽÃ'‚ ò üþôÃ'Æ'ûøÃ'€Ã¾Ã²Ã°Ã½Ã¸Ã¸ Ã'€Ã¾Ã'ÂÃ'‚ð Ã'ÂþÃ'ÂÃ'Æ'ôþò ò Ã'‚úðýÃ'ÂÃ'… ò ýþÃ'€Ã¼Ãµ ø ÿÃ'€Ã¸ Ã'€Ã°Ã·Ã»Ã¸Ã'‡Ã½Ã'‹Ã'… ÿðÃ'‚þûþóøÃ'‡ÃµÃ'ÂúøÃ'… Ã'ÂþÃ'ÂÃ'‚þÃ'ÂýøÃ'ÂÃ'…, ðÃ'ÂÃ'ÂþÃ'†Ã¸Ã¸Ã'€Ã¾Ã²Ã°Ã½Ã½Ã'‹Ã'… Ã' Ã°Ã±ÃµÃ'€Ã'€Ã°Ã½Ã'‚ýþù ýõþòðÃ'ÂúÃ'Æ'ûÃ'ÂÃ'€Ã¸Ã·Ã°Ã'†Ã¸ÃµÃ¹. æõûÃ'Å'Ã'Ž Ã'€Ã°Ã±Ã¾Ã'‚Ã'‹ ñÃ'‹Ã»Ã¾ þñþñÃ'‰ÃµÃ½Ã¸Ãµ øüõÃ'ŽÃ'‰ÃµÃ¹Ã'ÂÃ' Ã¸Ã½Ã'„þÃ'€Ã¼Ã°Ã'†Ã¸Ã¸, òúûÃ'ŽÃ'‡Ã°Ã' Ã'ÂþñÃ'ÂÃ'‚òõýýÃ'‹Ãµ Ã'ÂúÃ'ÂÿõÃ'€Ã¸Ã¼ÃµÃ½Ã'‚ðûÃ'Å'ýÃ'‹Ãµ ôðýýÃ'‹Ãµ ðòÃ'‚þÃ'€Ã¾Ã², þ ÿõÃ'€Ã'ÂÿõúÃ'‚øòðÃ'… ÿÃ'€Ã¸Ã¼ÃµÃ½ÃµÃ½Ã¸Ã' Ã°Ã½Ã³Ã¸Ã¾Ã'ÂÃ'‚ðÃ'‚øýþò ôûÃ' Ã»ÃµÃ'‡ÃµÃ½Ã¸Ã' Ã½ÃµÃ¾Ã²Ã°Ã'ÂúÃ'Æ'ûÃ'ÂÃ'€Ã½Ã'‹Ã'… ÷ðñþûõòðýøù óûð÷ð (ÃÂÃâ€"Ó). ÞÃ'Âýþòýþõ òýøüðýøõ Ã'ÂþÃ'ÂÃ'€ÃµÃ´Ã¾Ã'‚þÃ'‡ÃµÃ½Ã¾ ýð ÿðÃ'‚þûþóøÃ'ÂÃ'… Ã'ÂõÃ'‚Ã'‡Ã°Ã'‚úø ø ÿþòÃ'€ÃµÃ¶Ã´ÃµÃ½Ã¸Ã'ÂÃ'… Ã'€Ã¾Ã³Ã¾Ã²Ã¸Ã'†Ã'‹. Ã’ Ã'‡Ã°Ã'ÂÃ'‚ýþÃ'ÂÃ'‚ø, þÿøÃ'ÂÃ'‹Ã²Ã°Ã'ŽÃ'‚Ã'ÂÃ' Ã´Ã°Ã½Ã½Ã'‹Ãµ ûøÃ'‚õÃ'€Ã°Ã'‚Ã'Æ'Ã'€Ã'‹ þ ÿõÃ'€Ã'ÂÿõúÃ'‚øòýÃ'‹Ã'… ø Ã'€ÃµÃ'‚Ã'€Ã¾Ã'ÂÿõúÃ'‚øòýÃ'‹Ã'… øÃ'ÂÃ'ÂûõôþòðýøÃ'ÂÃ'…, úûøýøÃ'‡ÃµÃ'ÂúøÃ'… øÃ'ÂÿÃ'‹Ã'‚ðýøÃ'ÂÃ'… ø ÿðÃ'‚þÃ'„ø÷øþûþóøÃ'‡ÃµÃ'ÂúøÃ'… öøòþÃ'‚ýÃ'‹Ã'… üþôõûÃ'ÂÃ'…, Ã'Âþ÷ôðýýÃ'‹Ã'… ôûÃ' Ã¸Ã'ÂÃ'ÂûõôþòðýøÃ' Ã¸ ûõÃ'‡ÃµÃ½Ã¸Ã' ÃÂÃâ€"Ó. ÞÃ'ÂþñÃ'‹Ã¹ ðúÃ'†ÃµÃ½Ã'‚ ñÃ'‹Ã» Ã'Âôõûðý ýð ûðñþÃ'€Ã°Ã'‚þÃ'€Ã½Ã'‹Ã'… ÿþôÃ'…þôðÃ'… ú ÿþûÃ'Æ'Ã'‡ÃµÃ½Ã¸Ã'Ž Ã'€Ã°Ã·Ã»Ã¸Ã'‡Ã½Ã'‹Ã'… ø÷þÃ'„þÃ'€Ã¼ ðýóøþÃ'ÂÃ'‚ðÃ'‚øýð, ð Ã'‚ðúöõ ýð Ã'ÂÃ'€Ã°Ã²Ã½ÃµÃ½Ã¸Ã¸ ðýÃ'‚øðýóøþóõýýÃ'‹Ã'… òþ÷üþöýþÃ'ÂÃ'‚õù ýðÃ'‚øòýÃ'‹Ã'… ø Ã'€ µÃºÃ¾Ã¼Ã±Ã¸Ã½Ã°Ã½Ã'‚ýÃ'‹Ã'… ÿþûøÿõÿÃ'‚øôþòðýóøþÃ'ÂÃ'‚ðÃ'‚øýþò. àõ÷Ã'Æ'ûÃ'Å'Ã'‚ðÃ'‚Ã'‹ Ã'ÂõÃ'€Ã¸Ã¸ øÃ'ÂÃ'Âûõôþòðýøù Ã'ÂòøôõÃ'‚õûÃ'Å'Ã'ÂÃ'‚òÃ'Æ'Ã'ŽÃ'‚, Ã'‡Ã'‚þ ðýóøþÃ'ÂÃ'‚ðÃ'‚øýÃ'‹ üþóÃ'Æ'Ã'‚ ÿþûýþÃ'ÂÃ'‚Ã'Å'Ã'Ž Ã¿Ã¾Ã´Ã°Ã²Ã»Ã'ÂÃ'‚Ã'Å' ÿðÃ'‚þûþóøÃ'‡ÃµÃ'Âúøù ðýóøþóõýõ÷ ÿÃ'€Ã¸ ôøðñõÃ'‚øÃ'‡ÃµÃ'Âúþù ÿÃ'€Ã¾Ã»Ã¸Ã'„õÃ'€Ã°Ã'‚øòýþù Ã'€ÃµÃ'‚øýþÿðÃ'‚øø, ýõ òûøÃ'ÂÃ' Ã½Ã° ýþÃ'€Ã¼Ã°Ã
Texto completo: Disponível Coleções: Bases de dados de organismos internacionais Base of operations de dados: ProQuest Central Tipo de documento: Artigo Tipo de estudo: Estudo observacional / Fatores de risco Idioma: Inglês Revista: Biotechnologia Acta Ano de publicação: 2021
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Texto completo: Disponível Coleções: Bases de dados de organismos internacionais Base de dados: ProQuest Central Tipo de documento: Artigo Tipo de estudo: Estudo observacional / Fatores de risco Idioma: Inglês Revista: Biotechnologia Acta Ano de publicação: 2021
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