{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:52:52Z","timestamp":1781517172053,"version":"3.54.1"},"reference-count":51,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Discovery Eye Foundation, Polly and Michael Smith, Edith and Roy Carver","award":["ULI TR001414\/TR\/NCATS"],"award-info":[{"award-number":["ULI TR001414\/TR\/NCATS"]}]},{"name":"Iris and B. Gerald Cantor Foundation","award":["ULI TR001414\/TR\/NCATS"],"award-info":[{"award-number":["ULI TR001414\/TR\/NCATS"]}]},{"name":"Max Factor Family Foundation","award":["ULI TR001414\/TR\/NCATS"],"award-info":[{"award-number":["ULI TR001414\/TR\/NCATS"]}]},{"name":"NEI R01 EY027363 (MCK)","award":["ULI TR001414\/TR\/NCATS"],"award-info":[{"award-number":["ULI TR001414\/TR\/NCATS"]}]},{"name":"Unrestricted Departmental Grant","award":["ULI TR001414\/TR\/NCATS"],"award-info":[{"award-number":["ULI TR001414\/TR\/NCATS"]}]},{"name":"Institute for Clinical and Translational Science (ICTS) at the University of California","award":["ULI TR001414\/TR\/NCATS"],"award-info":[{"award-number":["ULI TR001414\/TR\/NCATS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study uses personalized chronic lymphoblastic leukemia (CLL) cybrid cells to test various drugs\/agents designed to improve mitochondrial function and cell longevity. Age-matched control (NL) and CLL cybrids were created. The NL and CLL cybrids were treated with ibrutinib (Ibr-10 \u03bcM), mitochondrial-targeted nutraceuticals such as alpha lipoic acid (ALA-1 mM), amla (Aml-300 \u03bcg), melatonin (Mel-1 mM), resveratrol (Res-100 \u03bcM) alone, or a combination of ibrutinib with nutraceuticals (Ibr + ALA, Ibr + Aml, Ibr + Mel, or Ibr + Res) for 48 h. MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliumbromide), H2DCFDA(2\u2032,7\u2032 Dichlorodihydrofluorescein diacetate), and JC1 assays were used to measure the cellular metabolism, intracellular ROS levels, and mitochondrial membrane potential (\u2206\u03c8m), respectively. The expression levels of genes associated with antioxidant enzymes (SOD2, GPX3, and NOX4), apoptosis (BAX and CASP3), and inflammation (IL6, IL-1\u03b2, TNF\u03b1, and TGF\u03b2) were measured using quantitative real-time PCR (qRT-PCR). CLL cybrids treated with Ibr + ALA, Ibr + Aml, Ibr + Mel, and Ibr + Res had (a) reduced cell survivability, (b) increased ROS production, (c) increased \u2206\u03c8m levels, (d) decreased antioxidant gene expression levels, and (e) increased apoptotic and inflammatory genes in CLL cybrids when compared with ibrutinib-alone-treated CLL cybrids. Our findings show that the addition of nutraceuticals makes the CLL cybrids more pro-apoptotic with decreased cell survival compared with CLL cybrids exposed to ibrutinib alone.<\/jats:p>","DOI":"10.3390\/ijms241311025","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T01:32:18Z","timestamp":1688434338000},"page":"11025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Using Human \u2018Personalized\u2019 Cybrids to Identify Drugs\/Agents That Can Regulate Chronic Lymphoblastic Leukemia Mitochondrial Dysfunction"],"prefix":"10.3390","volume":"24","author":[{"given":"Lata","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Department of Pediatrics, All India Institute of Medical Institute, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari","family":"Atilano","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Chwa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1812-9860","authenticated-orcid":false,"given":"Mithalesh K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Ozgul","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Nesburn","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Cristina","family":"Kenney","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1093\/annonc\/mdw547","article-title":"Management of chronic lymphocytic leukemia (CLL) in the elderly: A position paper from an international Society of Geriatric Oncology (SIOG) Task Force","volume":"28","author":"Stauder","year":"2017","journal-title":"Ann. 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