The Experts below are selected from a list of 1917 Experts worldwide ranked by ideXlab platform
Stephen C Pflugfelder - One of the best experts on this subject based on the ideXlab platform.
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protective effects of l carnitine against oxidative injury by hyperosmolarity in human corneal epithelial cells
Investigative Ophthalmology & Visual Science, 2015Co-Authors: Ruzhi Deng, Xia Hua, Wei Chi, Jing Lin, Stephen C PflugfelderAbstract:Dry eye is a multifactorial disease of the tears and ocular surface with symptoms of discomfort, visual disturbance, and tear film instability, which is often accompanied by tear film hyperosmolarity, inflammation of corneal and conjunctival epithelial cells, as well as decrease of conjunctival goblet cells and mucin production.1–5 Tear film hyperosmolarity has been considered as a key factor that initiates the ocular surface inflammation in dry-eye patients, as well as in mouse models.2,6–8 Our previous studies have also shown increased expression and production of proinflammatory cytokines (TNF-α, IL-1β, IL-6), chemokine (IL-8), and matrix metalloproteinases (MMP-13, -3, -9) in primary cultured human corneal epithelial cells (HCECs) exposed to hyperosmotic media.9–11 Current dry-eye therapies include tear supplementation, tear retention, tear volume stimulation, biological tear substitutes, antiinflammatory therapy, essential fatty acids, and environmental strategies, which improve dry-eye symptoms.12 However, many of them are palliative rather than disease-modifying, which often does not provide adequate symptom relief or prevent disease progression.13 Studies on pathogenic role of hyperosmolarity led to development of new preventive and therapeutic approaches to treat the patients with dry-eye syndrome. Osmoprotectants may become potential candidates based on their role in protecting cells from the effects of hyperosmolarity.6,14,15 Osmoprotectants are small organic molecules that are used in many cell types to restore isotonic cell volume and stabilize protein function, allowing adaptation to hyperosmolarity.6,16,17 Osmoprotectants are known as “organic osmolytes” or “compatible solutes,” and their uptake is accompanied by a decreasing concentration of intracellular inorganic salts.18–20 Recently, Osmoprotectants, L-carnitine, erythritol, and betaine, have been demonstrated to inhibit in HCECs and in a dry-eye mouse model hyperosmotic-induced increases in proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17) and chemokines (IL-8, CCL2, and CCL20).15,21 We further showed their suppressive effects on the expression, production, and activity of matrix metalloproteinases (MMP-13, MMP-2, MMP-9, MMP-3, and MMP-7) induced by hyperosmotic media in primary HCECs.22 We also observed that L-carnitine and erythritol protected HCECs from hyperosmotic stress via suppressive effect on activation of c-Jun N-terminal kinases (JNK) and p38MAP kinase.23 However, the mechanism of their protective effect on the ocular surface remains to be elucidated. Oxidative stress caused by overproduced reactive oxygen species (ROS) has been recognized to be an important mechanism involved in ocular surface inflammation and dry-eye disease, such as ROS-induced NLRP3 inflammasome activation, JNK pathway, CD95/CD95L apoptotic signaling activation, and so on.24–28 Reactive oxygen species are generated under normal physiological conditions from the mitochondrial electron transport chain and other sources, and play an important role in activating cellular signaling for survival. However, high levels of ROS cause oxidative stress and cell injury, including at least three reactions, lipid peroxidation of membranes, intracellular oxidative modification of proteins, and oxidative damage to DNA. These oxidative reactions form adducts with lipids, protein, and DNA, and lead to decreased functions of intracellular organelles and further damage.29,30 It is not clear whether and how hyperosmolarity induces oxidative injury to ocular surface epithelium. Here, we determined the protective cell defense effects of L-carnitine against oxidative damage induced by hyperosmotic stress in HCECs using an in vitro culture model of dry-eye disease.
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Osmoprotectants suppress the production and activity of matrix metalloproteinases induced by hyperosmolarity in primary human corneal epithelial cells
Molecular Vision, 2014Co-Authors: Ruzhi Deng, Xia Hua, Zongduan Zhang, Stephen C PflugfelderAbstract:Purpose Hyperosmolarity has been recognized as a proinflammatory stress in the pathogenesis of dry eye disease. This study investigated the suppressive effect of Osmoprotectants (L-carnitine, erythritol, and betaine) on the production and activity of matrix metalloproteinases (MMPs) in primary human corneal epithelial cells (HCECs) exposed to hyperosmotic stress.
Xia Hua - One of the best experts on this subject based on the ideXlab platform.
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protective effects of l carnitine against oxidative injury by hyperosmolarity in human corneal epithelial cells
Investigative Ophthalmology & Visual Science, 2015Co-Authors: Ruzhi Deng, Xia Hua, Wei Chi, Jing Lin, Stephen C PflugfelderAbstract:Dry eye is a multifactorial disease of the tears and ocular surface with symptoms of discomfort, visual disturbance, and tear film instability, which is often accompanied by tear film hyperosmolarity, inflammation of corneal and conjunctival epithelial cells, as well as decrease of conjunctival goblet cells and mucin production.1–5 Tear film hyperosmolarity has been considered as a key factor that initiates the ocular surface inflammation in dry-eye patients, as well as in mouse models.2,6–8 Our previous studies have also shown increased expression and production of proinflammatory cytokines (TNF-α, IL-1β, IL-6), chemokine (IL-8), and matrix metalloproteinases (MMP-13, -3, -9) in primary cultured human corneal epithelial cells (HCECs) exposed to hyperosmotic media.9–11 Current dry-eye therapies include tear supplementation, tear retention, tear volume stimulation, biological tear substitutes, antiinflammatory therapy, essential fatty acids, and environmental strategies, which improve dry-eye symptoms.12 However, many of them are palliative rather than disease-modifying, which often does not provide adequate symptom relief or prevent disease progression.13 Studies on pathogenic role of hyperosmolarity led to development of new preventive and therapeutic approaches to treat the patients with dry-eye syndrome. Osmoprotectants may become potential candidates based on their role in protecting cells from the effects of hyperosmolarity.6,14,15 Osmoprotectants are small organic molecules that are used in many cell types to restore isotonic cell volume and stabilize protein function, allowing adaptation to hyperosmolarity.6,16,17 Osmoprotectants are known as “organic osmolytes” or “compatible solutes,” and their uptake is accompanied by a decreasing concentration of intracellular inorganic salts.18–20 Recently, Osmoprotectants, L-carnitine, erythritol, and betaine, have been demonstrated to inhibit in HCECs and in a dry-eye mouse model hyperosmotic-induced increases in proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17) and chemokines (IL-8, CCL2, and CCL20).15,21 We further showed their suppressive effects on the expression, production, and activity of matrix metalloproteinases (MMP-13, MMP-2, MMP-9, MMP-3, and MMP-7) induced by hyperosmotic media in primary HCECs.22 We also observed that L-carnitine and erythritol protected HCECs from hyperosmotic stress via suppressive effect on activation of c-Jun N-terminal kinases (JNK) and p38MAP kinase.23 However, the mechanism of their protective effect on the ocular surface remains to be elucidated. Oxidative stress caused by overproduced reactive oxygen species (ROS) has been recognized to be an important mechanism involved in ocular surface inflammation and dry-eye disease, such as ROS-induced NLRP3 inflammasome activation, JNK pathway, CD95/CD95L apoptotic signaling activation, and so on.24–28 Reactive oxygen species are generated under normal physiological conditions from the mitochondrial electron transport chain and other sources, and play an important role in activating cellular signaling for survival. However, high levels of ROS cause oxidative stress and cell injury, including at least three reactions, lipid peroxidation of membranes, intracellular oxidative modification of proteins, and oxidative damage to DNA. These oxidative reactions form adducts with lipids, protein, and DNA, and lead to decreased functions of intracellular organelles and further damage.29,30 It is not clear whether and how hyperosmolarity induces oxidative injury to ocular surface epithelium. Here, we determined the protective cell defense effects of L-carnitine against oxidative damage induced by hyperosmotic stress in HCECs using an in vitro culture model of dry-eye disease.
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Osmoprotectants suppress the production and activity of matrix metalloproteinases induced by hyperosmolarity in primary human corneal epithelial cells
Molecular Vision, 2014Co-Authors: Ruzhi Deng, Xia Hua, Zongduan Zhang, Stephen C PflugfelderAbstract:Purpose Hyperosmolarity has been recognized as a proinflammatory stress in the pathogenesis of dry eye disease. This study investigated the suppressive effect of Osmoprotectants (L-carnitine, erythritol, and betaine) on the production and activity of matrix metalloproteinases (MMPs) in primary human corneal epithelial cells (HCECs) exposed to hyperosmotic stress.
Andrew D. Hanson - One of the best experts on this subject based on the ideXlab platform.
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betaines and related Osmoprotectants targets for metabolic engineering of stress resistance
Plant Physiology, 1999Co-Authors: Scott D Mcneil, Michael L Nuccio, Andrew D. HansonAbstract:Osmoprotectants (also termed compatible solutes) occur in all organisms from archaebacteria to higher plants and animals. They are highly soluble compounds that carry no net charge at physiological pH and are nontoxic at high concentrations. Osmoprotectants serve to raise osmotic pressure in the
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metabolic engineering of plants for osmotic stress resistance
Current Opinion in Plant Biology, 1999Co-Authors: Michael L Nuccio, David Rhodest, Scott D Mcneil, Andrew D. HansonAbstract:Genes encoding critical steps in the synthesis of Osmoprotectant compounds are now being expressed in transgenic plants. These plants generally accumulate low levels of Osmoprotectants and have increased stress tolerance. The next priority is therefore to engineer greater Osmoprotectant synthesis without detriment to the rest of metabolism. This will require manipulation of multiple genes, guided by thorough analysis of metabolite fluxes and pool sizes.
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osmoprotective compounds in the plumbaginaceae a natural experiment in metabolic engineering of stress tolerance
Proceedings of the National Academy of Sciences of the United States of America, 1994Co-Authors: Andrew D. Hanson, Jean Rivoal, Michael Burnet, Michael O Dillon, Bala Rathinasabapathi, Douglas A. GageAbstract:Abstract In common with other zwitterionic quarternary ammonium compounds (QACs), glycine betaine acts as an Osmoprotectant in plants, bacteria, and animals, with its accumulation in the cytoplasm reducing adverse effects of salinity and drought. For this reason, the glycine betaine biosynthesis pathway has become a target for genetic engineering of stress tolerance in crop plants. Besides glycine betaine, several other QAC Osmoprotectants have been reported to accumulate among flowering plants, although little is known about their distribution, evolution, or adaptive value. We show here that various taxa of the highly stress-tolerant family Plumbaginaceae have evolved four QACs, which supplement or replace glycine betaine-namely, choline O-sulfate and the betaines of beta-alanine, proline, and hydroxyproline. Evidence from bacterial bioassays demonstrates that these QACs function no better than glycine betaine as Osmoprotectants. However, the distribution of QACs among diverse members of the Plumbaginaceae adapted to different types of habitat indicates that different QACs could have selective advantages in particular stress environments. Specifically, choline O-sulfate can function in sulfate detoxification as well as in osmoprotection, beta-alanine betaine may be superior to glycine betaine in hypoxic saline conditions, and proline-derived betaines may be beneficial in chronically dry environments. We conclude that the evolution of Osmoprotectant diversity within the Plumbaginaceae suggests additional possibilities to explore in the metabolic engineering of stress tolerance in crops.
Ruzhi Deng - One of the best experts on this subject based on the ideXlab platform.
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protective effects of l carnitine against oxidative injury by hyperosmolarity in human corneal epithelial cells
Investigative Ophthalmology & Visual Science, 2015Co-Authors: Ruzhi Deng, Xia Hua, Wei Chi, Jing Lin, Stephen C PflugfelderAbstract:Dry eye is a multifactorial disease of the tears and ocular surface with symptoms of discomfort, visual disturbance, and tear film instability, which is often accompanied by tear film hyperosmolarity, inflammation of corneal and conjunctival epithelial cells, as well as decrease of conjunctival goblet cells and mucin production.1–5 Tear film hyperosmolarity has been considered as a key factor that initiates the ocular surface inflammation in dry-eye patients, as well as in mouse models.2,6–8 Our previous studies have also shown increased expression and production of proinflammatory cytokines (TNF-α, IL-1β, IL-6), chemokine (IL-8), and matrix metalloproteinases (MMP-13, -3, -9) in primary cultured human corneal epithelial cells (HCECs) exposed to hyperosmotic media.9–11 Current dry-eye therapies include tear supplementation, tear retention, tear volume stimulation, biological tear substitutes, antiinflammatory therapy, essential fatty acids, and environmental strategies, which improve dry-eye symptoms.12 However, many of them are palliative rather than disease-modifying, which often does not provide adequate symptom relief or prevent disease progression.13 Studies on pathogenic role of hyperosmolarity led to development of new preventive and therapeutic approaches to treat the patients with dry-eye syndrome. Osmoprotectants may become potential candidates based on their role in protecting cells from the effects of hyperosmolarity.6,14,15 Osmoprotectants are small organic molecules that are used in many cell types to restore isotonic cell volume and stabilize protein function, allowing adaptation to hyperosmolarity.6,16,17 Osmoprotectants are known as “organic osmolytes” or “compatible solutes,” and their uptake is accompanied by a decreasing concentration of intracellular inorganic salts.18–20 Recently, Osmoprotectants, L-carnitine, erythritol, and betaine, have been demonstrated to inhibit in HCECs and in a dry-eye mouse model hyperosmotic-induced increases in proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17) and chemokines (IL-8, CCL2, and CCL20).15,21 We further showed their suppressive effects on the expression, production, and activity of matrix metalloproteinases (MMP-13, MMP-2, MMP-9, MMP-3, and MMP-7) induced by hyperosmotic media in primary HCECs.22 We also observed that L-carnitine and erythritol protected HCECs from hyperosmotic stress via suppressive effect on activation of c-Jun N-terminal kinases (JNK) and p38MAP kinase.23 However, the mechanism of their protective effect on the ocular surface remains to be elucidated. Oxidative stress caused by overproduced reactive oxygen species (ROS) has been recognized to be an important mechanism involved in ocular surface inflammation and dry-eye disease, such as ROS-induced NLRP3 inflammasome activation, JNK pathway, CD95/CD95L apoptotic signaling activation, and so on.24–28 Reactive oxygen species are generated under normal physiological conditions from the mitochondrial electron transport chain and other sources, and play an important role in activating cellular signaling for survival. However, high levels of ROS cause oxidative stress and cell injury, including at least three reactions, lipid peroxidation of membranes, intracellular oxidative modification of proteins, and oxidative damage to DNA. These oxidative reactions form adducts with lipids, protein, and DNA, and lead to decreased functions of intracellular organelles and further damage.29,30 It is not clear whether and how hyperosmolarity induces oxidative injury to ocular surface epithelium. Here, we determined the protective cell defense effects of L-carnitine against oxidative damage induced by hyperosmotic stress in HCECs using an in vitro culture model of dry-eye disease.
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Osmoprotectants suppress the production and activity of matrix metalloproteinases induced by hyperosmolarity in primary human corneal epithelial cells
Molecular Vision, 2014Co-Authors: Ruzhi Deng, Xia Hua, Zongduan Zhang, Stephen C PflugfelderAbstract:Purpose Hyperosmolarity has been recognized as a proinflammatory stress in the pathogenesis of dry eye disease. This study investigated the suppressive effect of Osmoprotectants (L-carnitine, erythritol, and betaine) on the production and activity of matrix metalloproteinases (MMPs) in primary human corneal epithelial cells (HCECs) exposed to hyperosmotic stress.
I T Molinamartinez - One of the best experts on this subject based on the ideXlab platform.
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Osmoprotectants in hybrid liposome hpmc systems as potential glaucoma treatment
Polymers, 2019Co-Authors: Miguel Gomezballesteros, Jose Javier Lopezcano, Irene Bravoosuna, Rocio Herrerovanrell, I T MolinamartinezAbstract:The combination of acetazolamide-loaded nano-liposomes and Hydroxypropyl methylcellulose (HPMC) with similar components to the preocular tear film in an Osmoprotectant media (trehalose and erythritol) is proposed as a novel strategy to increase the ocular bioavailability of poorly soluble drugs. Ophthalmic formulations based on acetazolamide-loaded liposomes, dispersed in the Osmoprotectant solution (ACZ-LP) or in combination with HPMC (ACZ-LP-P) were characterized and in vivo evaluated. The pH and tonicity of both formulations resulted in physiological ranges. The inclusion of HPMC produced an increment in viscosity (from 0.9 to 4.7 mPa·s. 64.9 ± 2.6% of acetazolamide initially included in the formulation was retained in vesicles. In both formulations, a similar onset time (1 h) and effective time periods were observed (7 h) after a single instillation (25 μL) in normotensive rabbits' eyes. The AUC0-8h of the ACZ-LP-P was 1.5-fold higher than of ACZ-LP (p < 0.001) and the maximum hypotensive effect resulted in 1.4-fold higher (p < 0.001). In addition, the formulation of ACZ in the hybrid liposome/HPMC system produced a 30.25-folds total increment in ocular bioavailability, compared with the drug solution. Excellent tolerance in rabbits' eyes was confirmed during the study.
