المؤلفون: Asatryan, Aram, Calandria, Jorgelina M., Kautzmann, Marie-Audrey I., Jun, Bokkyoo, Gordon, William C., Do, Khanh V., Bhattacharjee, Surjyadipta, Pham, Thang L., Bermúdez, Vicente, Mateos, Melina Valeria, Heap, Jessica, Bazan, Nicolas G.

المساهمون: National Eye Institute

المصدر: Frontiers in Neuroscience ; volume 16 ; ISSN 1662-453X

مصطلحات موضوعية: General Neuroscience

الوصف: Retinal pigment epithelial (RPE) cells sustain photoreceptor integrity, and when this function is disrupted, retinal degenerations ensue. Herein, we characterize a new cell line from human RPE that we termed ABC . These cells remarkably recapitulate human eye native cells. Distinctive from other epithelia, RPE cells originate from the neural crest and follow a neural development but are terminally differentiated into “epithelial” type, thus sharing characteristics with their neuronal lineages counterparts. Additionally, they form microvilli, tight junctions, and honeycomb packing and express distinctive markers. In these cells, outer segment phagocytosis, phagolysosome fate, phospholipid metabolism, and lipid mediator release can be studied. ABC cells display higher resistance to oxidative stress and are protected from senescence through mTOR inhibition, making them more stable in culture. The cells are responsive to Neuroprotectin D1 (NPD1), which downregulates inflammasomes and upregulates antioxidant and anti-inflammatory genes. ABC gene expression profile displays close proximity to native RPE lineage, making them a reliable cell system to unravel signaling in uncompensated oxidative stress (UOS) and retinal degenerative disease to define neuroprotection sites.

الإتاحة: https://doi.org/10.3389/fnins.2022.926629Test

المؤلفون: Nguyen, Trang Huyen Thi, Le, Huong Thi, Le, Xuan Thi Thanh, Do, Toan Thanh Thi, Ngo, Toan Van, Phan, Hai Thanh, Vu, Giang Thu, Nguyen, Tu Huu, Phung, Dung Tri, Nghiem, Son Hong, Vu, Thuc Minh Thi, Nguyen, Thu Ha, Tran, Trung Dinh, Do, Khanh Nam, Truong, Dat Van, Le, Thanh Tuan, Tran, Bach Xuan, Latkin, Carl A., Ho, Roger C. M., Ho, Cyrus S. H.

المصدر: Frontiers in Public Health ; volume 10 ; ISSN 2296-2565

مصطلحات موضوعية: Public Health, Environmental and Occupational Health

الإتاحة: https://doi.org/10.3389/fpubh.2022.854543Test

المؤلفون: Patel, Manish, Jimeno, Antonio, Wang, Ding, Stemmer, Salomon, Bauer, Todd, Sweis, Randy, Geva, Ravit, Kummar, Shivaani, Reagan, Patrick, Perets, Ruth, LoRusso, Patricia, Gupta, Shilpa, Zacharek, Sima, Laino, Andressa, Milberg, Oleg, Frederick, Josh, Chen, Sheryl, Pascarella, Stephanie, Randolph, William, Aanur, Praveen, Johansen, Lisa, Do, Khanh, Meehan, Robert, Sullivan, Ryan

المصدر: Regular and Young Investigator Award Abstracts

الإتاحة: https://doi.org/10.1136/jitc-2021-sitc2021.539Test

المؤلفون: Nguyen, Trang Huyen Thi, Le, Huong Thi, Le, Xuan Thi Thanh, Do, Toan Thanh Thi, Ngo, Toan Van, Phan, Hai Thanh, Vu, Giang Thu, Nguyen, Tu Huu, Phung, Dung Tri, Nghiem, Son Hong, Vu, Thuc Minh Thi, Nguyen, Thu Ha, Tran, Trung Dinh, Do, Khanh Nam, Truong, Dat Van, Le, Thanh Tuan, Tran, Bach Xuan, Latkin, Carl A., Ho, Roger C. M., Ho, Cyrus S. H.

المساهمون: DEPT OF PSYCHOLOGICAL MEDICINE

المصدر: Scopus OA2021

مصطلحات موضوعية: coronavirus, hygiene practice, local preparedness, pandemic prevention, sanitation practice

الوصف: 10.3389/fpubh.2020.589183 ; Frontiers in Public Health ; 8 ; 589183

العلاقة: Nguyen, Trang Huyen Thi, Le, Huong Thi, Le, Xuan Thi Thanh, Do, Toan Thanh Thi, Ngo, Toan Van, Phan, Hai Thanh, Vu, Giang Thu, Nguyen, Tu Huu, Phung, Dung Tri, Nghiem, Son Hong, Vu, Thuc Minh Thi, Nguyen, Thu Ha, Tran, Trung Dinh, Do, Khanh Nam, Truong, Dat Van, Le, Thanh Tuan, Tran, Bach Xuan, Latkin, Carl A., Ho, Roger C. M., Ho, Cyrus S. H. (2021-01-26). Interdisciplinary Assessment of Hygiene Practices in Multiple Locations: Implications for COVID-19 Pandemic Preparedness in Vietnam. Frontiers in Public Health 8 : 589183. ScholarBank@NUS Repository. https://doi.org/10.3389/fpubh.2020.589183Test; https://scholarbank.nus.edu.sg/handle/10635/233280Test

الإتاحة: https://doi.org/10.3389/fpubh.2020.589183Test
https://scholarbank.nus.edu.sg/handle/10635/233280Test

المؤلفون: Miyagishima, Kiyoharu J., Sharma, Ruchi, Nimmagadda, Malika, Clore-Gronenborn, Katharina, Qureshy, Zoya, Ortolan, Davide, Bose, Devika, Farnoodian, Mitra, Zhang, Congxiao, Fausey, Andrew, Sergeev, Yuri V., Abu-Asab, Mones, Jun, Bokkyoo, Do, Khanh V., Kautzman Guerin, Marie Audrey, Calandria, Jorgelina, George, Aman, Guan, Bin, Wan, Qin, Sharp, Rachel C.

المصدر: School of Graduate Studies Faculty Publications

مصطلحات موضوعية: Medical Sciences, Medicine and Health Sciences, Neurosciences

الوصف: Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder caused by a missense substitution in CTRP5. Distinctive clinical features include sub-retinal pigment epithelium (RPE) deposits, choroidal neovascularization, and RPE atrophy. In induced pluripotent stem cells-derived RPE from L-ORD patients (L-ORD-iRPE), we show that the dominant pathogenic CTRP5 variant leads to reduced CTRP5 secretion. In silico modeling suggests lower binding of mutant CTRP5 to adiponectin receptor 1 (ADIPOR1). Downstream of ADIPOR1 sustained activation of AMPK renders it insensitive to changes in AMP/ATP ratio resulting in defective lipid metabolism, reduced Neuroprotectin D1(NPD1) secretion, lower mitochondrial respiration, and reduced ATP production. These metabolic defects result in accumulation of sub-RPE deposits and leave L-ORD-iRPE susceptible to dedifferentiation. Gene augmentation of L-ORD-iRPE with WT CTRP5 or modulation of AMPK, by metformin, re-sensitize L-ORD-iRPE to changes in cellular energy status alleviating the disease cellular phenotypes. Our data suggests a mechanism for the dominant behavior of CTRP5 mutation and provides potential treatment strategies for L-ORD patients.

وصف الملف: application/pdf

العلاقة: https://digitalscholar.lsuhsc.edu/sogs_facpubs/41Test; https://digitalscholar.lsuhsc.edu/context/sogs_facpubs/article/1040/viewcontent/KautzmanG_AMPKModulationAmelio_2021.pdfTest

الإتاحة: https://doi.org/10.1038/s42003-021-02872-xTest
https://digitalscholar.lsuhsc.edu/sogs_facpubs/41Test
https://digitalscholar.lsuhsc.edu/context/sogs_facpubs/article/1040/viewcontent/KautzmanG_AMPKModulationAmelio_2021.pdfTest

المؤلفون: Calandria, Jorgelina M., Bhattacharjee, Surjyadipta, Maness, Nicholas J., Kautzmann, Marie Audrey I., Asatryan, Aram, Gordon, William C., Do, Khanh V., Jun, Bokkyoo, Mukherjee, Pranab K., Petasis, Nicos A., Bazan, Nicolas G.

المصدر: School of Medicine Faculty Publications

مصطلحات موضوعية: Medical Specialties, Medicine and Health Sciences, Ophthalmology

الوصف: The pro-homeostatic lipid mediators elovanoids (ELVs) attenuate cell binding and entrance of the SARS-CoV-2 receptor-binding domain (RBD) as well as of the SARS-CoV-2 virus in human primary alveoli cells in culture. We uncovered that very-long-chain polyunsaturated fatty acid precursors (VLC-PUFA, n-3) activate ELV biosynthesis in lung cells. Both ELVs and their precursors reduce the binding to RBD. ELVs downregulate angiotensin-converting enzyme 2 (ACE2) and enhance the expression of a set of protective proteins hindering cell surface virus binding and upregulating defensive proteins against lung damage. In addition, ELVs and their precursors decreased the signal of spike (S) protein found in SARS-CoV-2 infected cells, suggesting that the lipids curb viral infection. These findings open avenues for potential preventive and disease-modifiable therapeutic approaches for COVID-19.

وصف الملف: application/pdf

العلاقة: https://digitalscholar.lsuhsc.edu/som_facpubs/193Test; https://digitalscholar.lsuhsc.edu/context/som_facpubs/article/1192/viewcontent/CalandriaM_ElovanoidsDownregulateSars_20210610.pdfTest

الإتاحة: https://doi.org/10.1038/s41598-021-91794-zTest
https://digitalscholar.lsuhsc.edu/som_facpubs/193Test
https://digitalscholar.lsuhsc.edu/context/som_facpubs/article/1192/viewcontent/CalandriaM_ElovanoidsDownregulateSars_20210610.pdfTest

المؤلفون: Pham, Thang L., He, Jiucheng, Kakazu, Azucena H., Calandria, Jorgelina, Do, Khanh V., Nshimiyimana, Robert, Lam, Ting F., Petasis, Nicos A., Bazan, Haydee E.P., Bazan, Nicolas G.

المصدر: School of Medicine Faculty Publications

مصطلحات موضوعية: Medical Specialties, Medicine and Health Sciences, Ophthalmology

الوصف: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable in society, triggering a public health crisis and economic collapse around the world. Effective treatments to mitigate this viral infection are needed. Since the eye is a route of virus entrance, we use an in vivo rat model of corneal inflammation as well as human corneal epithelial cells (HCEC) in culture challenged with IFNγ as models of the eye surface to study this issue. We explore ways to block the receptor-binding domain (RBD) of SARS-CoV-2 Spike (S) protein to angiotensin-converting enzyme 2 (ACE2). We found that the lipid mediators, elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i) decreased the expression of the ACE2 receptor, furin, and integrins in damaged corneas or IFNγ-stimulated HCEC. There was also a concomitant decrease in the binding of Spike RBD with the lipid treatments. Using RNA-seq analysis, we uncovered that the lipid mediators also attenuated the expression of pro-inflammatoy cytokines participating in hyper-inflammation and senescence programming. Thus, the bioactivity of these lipid mediators will contribute to open therapeutic avenues to counteract virus attachment and entrance to the body.

وصف الملف: application/pdf

العلاقة: https://digitalscholar.lsuhsc.edu/som_facpubs/192Test; https://digitalscholar.lsuhsc.edu/context/som_facpubs/article/1191/viewcontent/HeJ_ELV_N32AndRvD6Isomer_20210617.pdfTest

الإتاحة: https://doi.org/10.1038/s41598-021-92293-xTest
https://digitalscholar.lsuhsc.edu/som_facpubs/192Test
https://digitalscholar.lsuhsc.edu/context/som_facpubs/article/1191/viewcontent/HeJ_ELV_N32AndRvD6Isomer_20210617.pdfTest

المؤلفون: Das, Yannick, Swinkels, Daniëlle, Kocherlakota, Sai, Vinckier, Stefan, Vaz, Frédéric M., Wever, Eric, van Kampen, Antoine H.C., Jun, Bokkyoo, Do, Khanh V., Moons, Lieve, Bazan, Nicolas G., Van Veldhoven, Paul P, Baes, Myriam

المصدر: School of Medicine Faculty Publications

مصطلحات موضوعية: DHA, multifunctional protein 2, peroxisome, photoreceptors, PUFA, retina, β-oxidation, Medical Cell Biology, Medical Sciences, Medicine and Health Sciences

الوصف: Patients lacking multifunctional protein 2 (MFP2), the central enzyme of the peroxisomal β-oxidation pathway, develop retinopathy. This pathway is involved in the metabolism of very long chain (VLCFAs) and polyunsaturated (PUFAs) fatty acids, which are enriched in the photoreceptor outer segments (POS). The molecular mechanisms underlying the retinopathy remain, however, elusive. Here, we report that mice with MFP2 inactivation display decreased retinal function already at the age of 3 weeks, which is accompanied by a profound shortening of the photoreceptor outer and inner segments, but with preserved photoreceptor ultrastructure. Furthermore, MFP2 deficient retinas exhibit severe changes in gene expression with downregulation of genes involved in the phototransduction pathway and upregulation of inflammation related genes. Lipid profiling of the mutant retinas revealed a profound reduction of DHA-containing phospholipids. This was likely due to a hampered systemic supply and retinal traffic of this PUFA, although we cannot exclude that the local defect of peroxisomal β-oxidation contributes to this DHA decrease. Moreover, very long chain PUFAs were also reduced, with the exception of those containing ≥ 34 carbons that accumulated. The latter suggests that there is an uncontrollable elongation of retinal PUFAs. In conclusion, our data reveal that intact peroxisomal β-oxidation is indispensable for retinal integrity, most likely by maintaining PUFA homeostasis.

وصف الملف: application/pdf

العلاقة: https://digitalscholar.lsuhsc.edu/som_facpubs/7Test; https://digitalscholar.lsuhsc.edu/context/som_facpubs/article/1006/viewcontent/PeroxisomalMultifunctionalProtein2Deficiency_20210202.pdfTest

الإتاحة: https://doi.org/10.3389/fcell.2021.632930Test
https://digitalscholar.lsuhsc.edu/som_facpubs/7Test
https://digitalscholar.lsuhsc.edu/context/som_facpubs/article/1006/viewcontent/PeroxisomalMultifunctionalProtein2Deficiency_20210202.pdfTest

المؤلفون: Kummar, Shivaani, Srivastava, Apurva K., Navas, Tony, Cecchi, Fabiola, Lee, Young H., Bottaro, Donald P., Park, Sook Ryun, Do, Khanh T., Jeong, Woondong, Johnson, Barry C., Voth, Andrea R., Rubinstein, Larry, Wright, John J., Parchment, Ralph E., Doroshow, James H., Chen, Alice P.

المساهمون: National Cancer Institute

المصدر: Investigational New Drugs ; volume 39, issue 6, page 1577-1586 ; ISSN 0167-6997 1573-0646

مصطلحات موضوعية: Pharmacology (medical), Pharmacology, Oncology

الوصف: Summary The vascular endothelial growth factor (VEGF)/VEGFR and hepatocyte growth factor (HGF)/c-MET signaling pathways act synergistically to promote angiogenesis. Studies indicate VEGF inhibition leads to increased levels of phosphorylated c-MET, bypassing VEGF-mediated angiogenesis and leading to chemoresistance. We conducted a phase 1 clinical trial with 32 patients with refractory solid tumors to evaluate the safety, pharmacokinetics, and pharmacodynamics of combinations of VEGF-targeting pazopanib and the putative c-MET inhibitor ARQ197 (tivantinib) at 5 dose levels (DLs). Patients either took pazopanib and tivantinib from treatment initiation (escalation phase) or pazopanib alone for 7 days, with paired tumor sampling, prior to starting combination treatment (expansion phase). Hypertension was the most common adverse event. No more than 1 dose limiting toxicity (DLT) occurred at any DL, so the maximum tolerated dose (MTD) was not determined; DL5 (800 mg pazopanib daily and 360 mg tivantinib BID) was used during the expansion phase. Twenty of 31 evaluable patients achieved stable disease lasting up to 22 cycles. Circulating VEGF, VEGFR2, HGF, and c-MET levels were assessed, and only VEGF levels increased. Tumor c-MET levels (total and phosphorylated) were determined in paired biopsies before and after 7 days of pazopanib treatment. Total intact c-MET decreased in 6 of 7 biopsy pairs, in contrast to previously reported c-MET elevation in response to VEGF inhibition. These results are discussed in the context of our previously reported analysis of epithelial-mesenchymal transition in these tumors.

الإتاحة: https://doi.org/10.1007/s10637-021-01138-xTest

المؤلفون: Emre, Ceren, Do, Khanh V., Jun, Bokkyoo, Hjorth, Erik, Alcalde, Silvia Gómez, Kautzmann, Marie-Audrey I., Gordon, William C., Nilsson, Per, Bazan, Nicolas G., Schultzberg, Marianne

المساهمون: Vetenskapsrådet, Alzheimerfonden, Åhlén-stiftelsen, Gun och Bertil Stohnes Stiftelse, Stiftelsen för Gamla Tjänarinnor, Torsten Söderbergs Stiftelse, Bertil Hållstens Forskningsstiftelse, EENT foundation, Karolinska Institute

المصدر: Acta Neuropathologica Communications ; volume 9, issue 1 ; ISSN 2051-5960

مصطلحات موضوعية: Cellular and Molecular Neuroscience, Neurology (clinical), Pathology and Forensic Medicine

الوصف: Sustained brain chronic inflammation in Alzheimer’s disease (AD) includes glial cell activation, an increase in cytokines and chemokines, and lipid mediators (LMs), concomitant with decreased pro-homeostatic mediators. The inflammatory response at the onset of pathology engages activation of pro-resolving, pro-homeostatic LMs followed by a gradual decrease. We used an APP knock-in ( App KI) AD mouse that accumulates β-amyloid (Aβ) and presents cognitive deficits (at 2 and 6 months of age, respectively) to investigate LMs, their precursors, biosynthetic enzymes and receptors, glial activation, and inflammatory proteins in the cerebral cortex and hippocampus at 2-, 4-, 8- and 18-month-old in comparison with wild-type (WT) mice. We used LC-mass-spectrometry and MALDI molecular imaging to analyze LMs and phospholipids, and immunochemistry for proteins. Our results revealed an age-specific lipid and cytokine profile, and glial activation in the App KI mice. Despite an early onset of Aβ pathology, pro-inflammatory and pro-resolving LMs were prominently increased only in the oldest age group. Furthermore, the LM biosynthetic enzymes increased, and their receptor expression decreased in the aged App KI mice. Arachidonic acid (AA)-containing phospholipid molecular species were elevated, correlating with decreased cPLA2 activity. MALDI molecular imaging depicted differential distribution of phospholipids according to genotype in hippocampal layers. Brain histology disclosed increased microglia proliferation starting from young age in the App KI mice, while astrocyte numbers were enhanced in older ages. Our results demonstrate that the brain lipidome is modified preferentially during aging as compared to amyloid pathology in the model studied here. However, alterations in phospholipids signal early pathological changes in membrane composition.

الإتاحة: https://doi.org/10.1186/s40478-021-01216-4Test