24 results on '"Premranjan Kumar"'
Search Results
2. Mechanistic Role of Jak3 in Obesity-Associated Cognitive Impairments
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Premranjan Kumar, Jayshree Mishra, and Narendra Kumar
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high-fat diet ,obesity ,Janus kinase-3 ,TREM-2 ,microglia ,cognitive impairments ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Background and Aims: A compromise in intestinal mucosal functions is associated with several chronic inflammatory diseases. Previously, we reported that obese humans have a reduced expression of intestinal Janus kinase-3 (Jak3), a non-receptor tyrosine kinase, and a deficiency of Jak3 in mice led to predisposition to obesity-associated metabolic syndrome. Since meta-analyses show cognitive impairment as co-morbidity of obesity, the present study demonstrates the mechanistic role of Jak3 in obesity associated cognitive impairment. Our data show that high-fat diet (HFD) suppresses Jak3 expression both in intestinal mucosa and in the brain of wild-type mice. Methodology: Recapitulating these conditions using global (Jak3-KO) and intestinal epithelial cell-specific conditional (IEC-Jak3-KO) mice and using cognitive testing, western analysis, flow cytometry, immunofluorescence microscopy and 16s rRNA sequencing, we demonstrate that HFD-induced Jak3 deficiency is responsible for cognitive impairments in mice, and these are, in part, specifically due to intestinal epithelial deficiency of Jak3. Results: We reveal that Jak3 deficiency leads to gut dysbiosis, compromised TREM-2-functions-mediated activation of microglial cells, increased TLR-4 expression and HIF1-α-mediated inflammation in the brain. Together, these lead to compromised microglial-functions-mediated increased deposition of β-amyloid (Aβ) and hyperphosphorylated Tau (pTau), which are responsible for cognitive impairments. Collectively, these data illustrate how the drivers of obesity promote cognitive impairment and demonstrate the underlying mechanism where HFD-mediated impact on IEC-Jak3 deficiency is responsible for Jak3 deficiency in the brain, reduced microglial TREM2 expression, microglial activation and compromised clearance of Aβ and pTau as the mechanism during obesity-associated cognitive impairments. Conclusion: Thus, we not only demonstrate the mechanism of obesity-associated cognitive impairments but also characterize the tissue-specific role of Jak3 in such conditions through mucosal tolerance, gut–brain axis and regulation of microglial functions.
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- 2022
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3. Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial
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Premranjan Kumar, Chun Liu, Jean W. Hsu, Shaji Chacko, Charles Minard, Farook Jahoor, and Rajagopal V. Sekhar
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aging ,cognition ,inflammation ,insulin resistance ,mitochondria ,oxidative stress ,Medicine (General) ,R5-920 - Abstract
Abstract Background Oxidative stress (OxS) and mitochondrial dysfunction are implicated as causative factors for aging. Older adults (OAs) have an increased prevalence of elevated OxS, impaired mitochondrial fuel‐oxidation (MFO), elevated inflammation, endothelial dysfunction, insulin resistance, cognitive decline, muscle weakness, and sarcopenia, but contributing mechanisms are unknown, and interventions are limited/lacking. We previously reported that inducing deficiency of the antioxidant tripeptide glutathione (GSH) in young mice results in mitochondrial dysfunction, and that supplementing GlyNAC (combination of glycine and N‐acetylcysteine [NAC]) in aged mice improves naturally‐occurring GSH deficiency, mitochondrial impairment, OxS, and insulin resistance. This pilot trial in OA was conducted to test the effect of GlyNAC supplementation and withdrawal on intracellular GSH concentrations, OxS, MFO, inflammation, endothelial function, genotoxicity, muscle and glucose metabolism, body composition, strength, and cognition. Methods A 36‐week open‐label clinical trial was conducted in eight OAs and eight young adults (YAs). After all the participants underwent an initial (pre‐supplementation) study, the YAs were released from the study. OAs were studied again after GlyNAC supplementation for 24 weeks, and GlyNAC withdrawal for 12 weeks. Measurements included red‐blood cell (RBC) GSH, MFO; plasma biomarkers of OxS, inflammation, endothelial function, glucose, and insulin; gait‐speed, grip‐strength, 6‐min walk test; cognitive tests; genomic‐damage; glucose‐production and muscle‐protein breakdown rates; and body‐composition. Results GlyNAC supplementation for 24 weeks in OA corrected RBC‐GSH deficiency, OxS, and mitochondrial dysfunction; and improved inflammation, endothelial dysfunction, insulin‐resistance, genomic‐damage, cognition, strength, gait‐speed, and exercise capacity; and lowered body‐fat and waist‐circumference. However, benefits declined after stopping GlyNAC supplementation for 12 weeks. Conclusions GlyNAC supplementation for 24‐weeks in OA was well tolerated and lowered OxS, corrected intracellular GSH deficiency and mitochondrial dysfunction, decreased inflammation, insulin‐resistance and endothelial dysfunction, and genomic‐damage, and improved strength, gait‐speed, cognition, and body composition. Supplementing GlyNAC in aging humans could be a simple and viable method to promote health and warrants additional investigation.
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- 2021
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4. GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage
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Premranjan Kumar, Ob W. Osahon, and Rajagopal V. Sekhar
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GlyNAC ,lifespan ,oxidative stress ,oxidant damage ,mitochondria ,mitophagy ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Determinants of length of life are not well understood, and therefore increasing lifespan is a challenge. Cardinal theories of aging suggest that oxidative stress (OxS) and mitochondrial dysfunction contribute to the aging process, but it is unclear if they could also impact lifespan. Glutathione (GSH), the most abundant intracellular antioxidant, protects cells from OxS and is necessary for maintaining mitochondrial health, but GSH levels decline with aging. Based on published human studies where we found that supplementing glycine and N-acetylcysteine (GlyNAC) improved/corrected GSH deficiency, OxS and mitochondrial dysfunction, we hypothesized that GlyNAC supplementation could increase longevity. We tested our hypothesis by evaluating the effect of supplementing GlyNAC vs. placebo in C57BL/6J mice on (a) length of life; and (b) age-associated GSH deficiency, OxS, mitochondrial dysfunction, abnormal mitophagy and nutrient-sensing, and genomic-damage in the heart, liver and kidneys. Results showed that mice receiving GlyNAC supplementation (1) lived 24% longer than control mice; (2) improved/corrected impaired GSH synthesis, GSH deficiency, OxS, mitochondrial dysfunction, abnormal mitophagy and nutrient-sensing, and genomic-damage. These studies provide proof-of-concept that GlyNAC supplementation can increase lifespan and improve multiple age-associated defects. GlyNAC could be a novel and simple nutritional supplement to improve lifespan and healthspan, and warrants additional investigation.
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- 2022
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5. Severe Glutathione Deficiency, Oxidative Stress and Oxidant Damage in Adults Hospitalized with COVID-19: Implications for GlyNAC (Glycine and N-Acetylcysteine) Supplementation
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Premranjan Kumar, Ob Osahon, David B. Vides, Nicola Hanania, Charles G. Minard, and Rajagopal V. Sekhar
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COVID-19 ,glutathione ,oxidative stress ,oxidant damage ,GlyNAC ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Humanity is battling a respiratory pandemic pneumonia named COVID-19 which has resulted in millions of hospitalizations and deaths. COVID-19 exacerbations occur in waves that continually challenge healthcare systems globally. Therefore, there is an urgent need to understand all mechanisms by which COVID-19 results in health deterioration to facilitate the development of protective strategies. Oxidative stress (OxS) is a harmful condition caused by excess reactive-oxygen species (ROS) and is normally neutralized by antioxidants among which Glutathione (GSH) is the most abundant. GSH deficiency results in amplified OxS due to compromised antioxidant defenses. Because little is known about GSH or OxS in COVID-19 infection, we measured GSH, TBARS (a marker of OxS) and F2-isoprostane (marker of oxidant damage) concentrations in 60 adult patients hospitalized with COVID-19. Compared to uninfected controls, COVID-19 patients of all age groups had severe GSH deficiency, increased OxS and elevated oxidant damage which worsened with advancing age. These defects were also present in younger age groups, where they do not normally occur. Because GlyNAC (combination of glycine and N-acetylcysteine) supplementation has been shown in clinical trials to rapidly improve GSH deficiency, OxS and oxidant damage, GlyNAC supplementation has implications for combating these defects in COVID-19 infected patients and warrants urgent investigation.
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- 2021
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6. Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial
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Premranjan Kumar, Chun Liu, James W. Suliburk, Charles G. Minard, Raja Muthupillai, Shaji Chacko, Jean W. Hsu, Farook Jahoor, and Rajagopal V. Sekhar
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premature aging ,HIV ,mitochondrial function ,oxidative stress ,GlyNAC ,Glutathione ,Biology (General) ,QH301-705.5 - Abstract
Background: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributing mechanisms are unclear and interventions are lacking. We hypothesized that deficiency of the antioxidant protein glutathione (GSH) contributes to multiple defects representing premature aging in PWH, and that these defects could be improved by supplementing the GSH precursors glycine and N-acetylcysteine (GlyNAC). Methods: We conducted an open label clinical trial where eight PWH and eight matched uninfected-controls were studied at baseline. PWH were studied again 12-weeks after receiving GlyNAC, and 8-weeks after stopping GlyNAC. Controls did not receive supplementation. Outcome measures included red-blood cell and muscle GSH concentrations, mitochondrial function, mitophagy and autophagy, oxidative stress, inflammation, endothelial function, genomic damage, insulin resistance, glucose production, muscle-protein breakdown rates, body composition, physical function and cognition. Results: PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. Conclusions: This open label trial finds that PWH have premature aging based on multiple biological and functional defects, and identifies novel mechanistic explanations for cognitive and physical decline. Nutritional supplementation with GlyNAC improves comorbidities suggestive of premature aging in PWH including functional and cognitive decline, and warrants additional investigation.
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- 2020
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7. Emerging Prevention and Treatment Strategies to Control COVID-19
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Vipul K. Singh, Abhishek Mishra, Shubhra Singh, Premranjan Kumar, Manisha Singh, Chinnaswamy Jagannath, and Arshad Khan
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COVID-19 ,SARS-CoV-2 ,drug repurposing ,vaccine interventions ,convalescent plasma ,stem cell therapy ,Medicine - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has now become a serious global threat after inflicting more than 8 million infections and 425,000 deaths in less than 6 months. Currently, no definitive treatment or prevention therapy exists for COVID-19. The unprecedented rise of this pandemic has rapidly fueled research efforts to discover and develop new vaccines and treatment strategies against this novel coronavirus. While hundreds of vaccines/therapeutics are still in the preclinical or early stage of clinical development, a few of them have shown promising results in controlling the infection. Here, in this review, we discuss the promising vaccines and treatment options for COVID-19, their challenges, and potential alternative strategies.
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- 2020
- Full Text
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8. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial
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Premranjan Kumar, Chun Liu, James Suliburk, Jean W Hsu, Raja Muthupillai, Farook Jahoor, Charles G Minard, George E Taffet, and Rajagopal V Sekhar
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Aging ,Geriatrics and Gerontology - Abstract
Background Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial. Methods Twenty-four OA and 12 young adults (YA) were studied. OA was randomized to receive either GlyNAC (N = 12) or isonitrogenous alanine placebo (N = 12) for 16-weeks; YA (N = 12) received GlyNAC for 2-weeks. Participants were studied before, after 2-weeks, and after 16-weeks of supplementation to assess GSH concentrations, OxS, MFO, molecular regulators of energy metabolism, inflammation, endothelial function, IR, aging hallmarks, gait speed, muscle strength, 6-minute walk test, body composition, and blood pressure. Results Compared to YA, OA had GSH deficiency, OxS, mitochondrial dysfunction (with defective molecular regulation), inflammation, endothelial dysfunction, IR, multiple aging hallmarks, impaired physical function, increased waist circumference, and systolic blood pressure. GlyNAC (and not placebo) supplementation in OA improved/corrected these defects. Conclusion GlyNAC supplementation in OA for 16-weeks was safe and well-tolerated. By combining the benefits of glycine, NAC and GSH, GlyNAC is an effective nutritional supplement that improves and reverses multiple age-associated abnormalities to promote health in aging humans. Clinical Trials Registration Number: NCT01870193
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- 2022
9. SUPPLEMENTING GLYNAC IN AGING IMPROVES GLUTATHIONE, MITOCHONDRIA, AND AGING HALLMARKS: A RANDOMIZED CLINICAL TRIAL
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Rajagopal Sekhar, Premranjan Kumar, Chun Liu, James Suliburk, Jean Hsu, Farook Jahoor, Charles Minard, and George Taffet
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Health (social science) ,Life-span and Life-course Studies ,Health Professions (miscellaneous) - Abstract
Oxidative stress (OxS), mitochondrial dysfunction and aging hallmarks are important contributors to aging, but effective solutions to correct these defects in older adults (OA) are lacking. Via earlier translational studies we discovered that supplementation of GlyNAC (combination of glycine and N-acetylcysteine) improves/corrects these defects. We conducted a double-blind, placebo-controlled (RCT) in 24 OA (mean age 71y) to definitively determine the effects of supplementing GlyNAC vs. isonitrogenous placebo (alanine) for 16-weeks on intracellular glutathione (GSH), OxS mitochondrial function, inflammation, insulin-resistance, endothelial function, physical function, body composition and multiple aging hallmarks. 12 YA (mean age 25y) served as young controls and received GlyNAC for 2-weeks. Subjects were studied before receiving supplementation study, and after receiving supplementation for 2-weeks (OA, YA) and 16-weeks (OA). The RCT found that compared to YA, the OA had severe GSH deficiency (red-cells, muscle), mitochondrial dysfunction, OxS (TBARS, F2-isoprostanes), diminished physical function (gait-speed, muscle strength, exercise capacity), elevated waist-circumference and systolic blood pressure, and multiple hallmarks defects of aging (affecting mitochondrial function, mitophagy, nutrient sensing, inflammation, insulin-resistance, genotoxicity, stem-cells and cellular senescence). GlyNAC supplementation for 2-weeks rapidly improved several defects, and further improved/corrected multiple defects after 16-weeks. No improvements were seen in YA receiving GlyNAC, or in OA receiving the alanine placebo, suggesting that protein supplementation per se in OA does not improve defects. The results of this RCT provides proof-of-concept that GlyNAC supplementation improves/reverses GSH deficiency, mitochondrial dysfunction, OxS, inflammation, physical function/strength and multiple aging hallmarks. GlyNAC could be a novel, simple and safe nutritional supplement to improve/reverse age-associated defects and promote health in aging humans.
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- 2022
10. Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial
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Rajagopal V. Sekhar, Farook Jahoor, Premranjan Kumar, Chun Liu, Jean W. Hsu, Shaji Chacko, and Charles G. Minard
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cognition ,Male ,0301 basic medicine ,Aging ,medicine.medical_treatment ,Medicine (miscellaneous) ,Pilot Projects ,medicine.disease_cause ,Acetylcysteine ,0302 clinical medicine ,insulin resistance ,oxidative stress ,Endothelial dysfunction ,Cognitive decline ,Research Articles ,Aged, 80 and over ,lcsh:R5-920 ,Age Factors ,Glycine Agents ,Free Radical Scavengers ,Glutathione ,Mitochondria ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,medicine.symptom ,lcsh:Medicine (General) ,strength ,Research Article ,medicine.drug ,Adult ,medicine.medical_specialty ,Glycine ,Inflammation ,Young Adult ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,medicine ,Humans ,Endothelium ,Muscle Strength ,Geriatric Assessment ,Aged ,business.industry ,Insulin ,medicine.disease ,030104 developmental biology ,Endocrinology ,Sarcopenia ,Dietary Supplements ,business ,Oxidative stress ,DNA Damage - Abstract
Background Oxidative stress (OxS) and mitochondrial dysfunction are implicated as causative factors for aging. Older adults (OAs) have an increased prevalence of elevated OxS, impaired mitochondrial fuel‐oxidation (MFO), elevated inflammation, endothelial dysfunction, insulin resistance, cognitive decline, muscle weakness, and sarcopenia, but contributing mechanisms are unknown, and interventions are limited/lacking. We previously reported that inducing deficiency of the antioxidant tripeptide glutathione (GSH) in young mice results in mitochondrial dysfunction, and that supplementing GlyNAC (combination of glycine and N‐acetylcysteine [NAC]) in aged mice improves naturally‐occurring GSH deficiency, mitochondrial impairment, OxS, and insulin resistance. This pilot trial in OA was conducted to test the effect of GlyNAC supplementation and withdrawal on intracellular GSH concentrations, OxS, MFO, inflammation, endothelial function, genotoxicity, muscle and glucose metabolism, body composition, strength, and cognition. Methods A 36‐week open‐label clinical trial was conducted in eight OAs and eight young adults (YAs). After all the participants underwent an initial (pre‐supplementation) study, the YAs were released from the study. OAs were studied again after GlyNAC supplementation for 24 weeks, and GlyNAC withdrawal for 12 weeks. Measurements included red‐blood cell (RBC) GSH, MFO; plasma biomarkers of OxS, inflammation, endothelial function, glucose, and insulin; gait‐speed, grip‐strength, 6‐min walk test; cognitive tests; genomic‐damage; glucose‐production and muscle‐protein breakdown rates; and body‐composition. Results GlyNAC supplementation for 24 weeks in OA corrected RBC‐GSH deficiency, OxS, and mitochondrial dysfunction; and improved inflammation, endothelial dysfunction, insulin‐resistance, genomic‐damage, cognition, strength, gait‐speed, and exercise capacity; and lowered body‐fat and waist‐circumference. However, benefits declined after stopping GlyNAC supplementation for 12 weeks. Conclusions GlyNAC supplementation for 24‐weeks in OA was well tolerated and lowered OxS, corrected intracellular GSH deficiency and mitochondrial dysfunction, decreased inflammation, insulin‐resistance and endothelial dysfunction, and genomic‐damage, and improved strength, gait‐speed, cognition, and body composition. Supplementing GlyNAC in aging humans could be a simple and viable method to promote health and warrants additional investigation., This study found that compared to healthy young adults, older humans have severely elevated oxidative stress, glutathione deficiency, impaired mitochondrial function, increased inflammation, insulin resistance and endothelial dysfunction, and lower muscle strength and mental cognition. We tested and found that supplementing GlyNAC (combination of glycine and N‐acetylcysteine) improved all these defects, and that stopping GlyNAC resulted in a loss of benefits. The results of this trial suggests that GlyNAC supplementation could be a simple, safe and effective nutritional strategy to boost cellular defenses to protect against oxidative stress, correct mitochondrial defects to improve energy availability, increase muscle strength and cognition, and thereby promote healthy aging in humans.
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- 2021
11. Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial
- Author
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Shaji Chacko, Rajagopal V. Sekhar, Raja Muthupillai, Chun Liu, James W. Suliburk, Premranjan Kumar, Charles G. Minard, Jean W. Hsu, and Farook Jahoor
- Subjects
0301 basic medicine ,Oncology ,Premature aging ,cognition ,medicine.medical_specialty ,Nutritional Supplementation ,Medicine (miscellaneous) ,medicine.disease_cause ,GlyNAC ,General Biochemistry, Genetics and Molecular Biology ,Article ,Acetylcysteine ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,physical function ,mitochondrial function ,Internal medicine ,Mitophagy ,medicine ,oxidative stress ,Cognitive decline ,Endothelial dysfunction ,lcsh:QH301-705.5 ,business.industry ,premature aging ,HIV ,medicine.disease ,Glutathione ,030104 developmental biology ,lcsh:Biology (General) ,business ,030217 neurology & neurosurgery ,Oxidative stress ,medicine.drug - Abstract
Background: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributing mechanisms are unclear and interventions are lacking. We hypothesized that deficiency of the antioxidant protein glutathione (GSH) contributes to multiple defects representing premature aging in PWH, and that these defects could be improved by supplementing the GSH precursors glycine and N-acetylcysteine (GlyNAC). Methods: We conducted an open label clinical trial where eight PWH and eight matched uninfected-controls were studied at baseline. PWH were studied again 12-weeks after receiving GlyNAC, and 8-weeks after stopping GlyNAC. Controls did not receive supplementation. Outcome measures included red-blood cell and muscle GSH concentrations, mitochondrial function, mitophagy and autophagy, oxidative stress, inflammation, endothelial function, genomic damage, insulin resistance, glucose production, muscle-protein breakdown rates, body composition, physical function and cognition. Results: PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. Conclusions: This open label trial finds that PWH have premature aging based on multiple biological and functional defects, and identifies novel mechanistic explanations for cognitive and physical decline. Nutritional supplementation with GlyNAC improves comorbidities suggestive of premature aging in PWH including functional and cognitive decline, and warrants additional investigation.
- Published
- 2020
12. Emerging Prevention and Treatment Strategies to Control COVID-19
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Shubhra Singh, Chinnaswamy Jagannath, Manisha Singh, Abhishek Mishra, Premranjan Kumar, Arshad Khan, and Vipul K. Singh
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Microbiology (medical) ,medicine.medical_specialty ,Convalescent plasma ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,lcsh:Medicine ,Review ,medicine.disease_cause ,stem cell therapy ,vaccine interventions ,Pandemic ,medicine ,Immunology and Allergy ,Intensive care medicine ,Molecular Biology ,Coronavirus ,General Immunology and Microbiology ,drug repurposing ,business.industry ,SARS-CoV-2 ,lcsh:R ,Treatment options ,COVID-19 ,Drug repositioning ,Infectious Diseases ,convalescent plasma ,Treatment strategy ,business - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has now become a serious global threat after inflicting more than 8 million infections and 425,000 deaths in less than 6 months. Currently, no definitive treatment or prevention therapy exists for COVID-19. The unprecedented rise of this pandemic has rapidly fueled research efforts to discover and develop new vaccines and treatment strategies against this novel coronavirus. While hundreds of vaccines/therapeutics are still in the preclinical or early stage of clinical development, a few of them have shown promising results in controlling the infection. Here, in this review, we discuss the promising vaccines and treatment options for COVID-19, their challenges, and potential alternative strategies.
- Published
- 2020
13. Reversing Mitochondrial, Metabolic and Molecular Defects in the Brain Improves Cognition in Aged Mice
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Premranjan Kumar and Rajagopal V. Sekhar
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Abstracts ,Health (social science) ,business.industry ,Medicine ,Session 7715 (Symposium) ,Reversing ,Cognition ,AcademicSubjects/SOC02600 ,Life-span and Life-course Studies ,business ,Health Professions (miscellaneous) ,Neuroscience - Abstract
Age-associated cognitive-decline is a risk factor for Alzheimer’s disease (AD), but mechanisms are not well understood, and interventions are lacking. Rodent studies on AD have not led to therapeutic breakthroughs for cognitively-impaired humans. In an open-label trial in older-adults we found that supplementing GlyNAC (glutathione precursors glycine and N-acetylcysteine) improved cognitive-decline, defects in whole-body mitochondrial-function, and systemic insulin-resistance, oxidative-stress, and inflammation. We hypothesized that aged-mice will have similar defects in the brain, and studied male C57BL/6J mice as follows: young-mice (20w) were compared to two-groups of aged-mice (90-weeks) receiving either GlyNAC or isonitrogenous-placebo diets for 8-weeks. GlyNAC-supplementation improved cognition, and the following measures in the brain: glutathione-concentrations, glucose-transporters in blood-brain-barrier and neurons, mitochondrial glucose-oxidation, oxidative-stress, endoplasmic-reticulum stress, autophagy, mitophagy, inflammation, senescence, genomic and telomere damage. These data provide mechanistic insights into the novel and beneficial role of GlyNAC supplementation to reverse cognitive-decline in aging, and holds promise for human AD.
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- 2020
14. Reversing cognitive-decline in older adults in an open-label clinical trial: novel mechanisms and the role of GlyNAC
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Premranjan Kumar, Rajagopal V. Sekhar, Charles G. Minard, Chun Liu, and Shaji Chacko
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medicine.medical_specialty ,Health (social science) ,business.industry ,Session 7715 (Symposium) ,Health Professions (miscellaneous) ,Clinical trial ,Abstracts ,Physical medicine and rehabilitation ,Medicine ,Reversing ,Cognitive decline ,Open label ,Life-span and Life-course Studies ,business ,AcademicSubjects/SOC02600 - Abstract
Age-associated cognitive-decline is an important risk factor for Alzheimer’s disease, but interventions are lacking. We conducted an open-label trial to test our hypotheses on whether: (1) compared to 8 healthy young adults (25y), 8 ‘healthy’ older adults (74y) have cognitive decline, decreased glucose availability for the brain due to mitochondrial dysfunction, elevated insulin-resistance, oxidative-stress and elevated inflammation; (2) supplementing glycine and N-acetylcysteine (GlyNAC) for 24-weeks corrects deficiency of the endogenous-antioxidant Glutathione and improves these defects, and thereby cognition; (3) stopping GlyNAC supplementation for 12-weeks results in a decline in accrued benefits. Outcome measures included cognitive testing (Montreal cognitive assessment; trail-making tests; verbal-fluency tests; digital-symbol substitution-test), mitochondrial fuel-oxidation, RBC-Glutathione concentrations, plasma oxidative-stress, insulin-resistance and inflammation, and tracer-studies to measure glucose metabolism. Results validated our hypotheses and showed that GlyNAC-supplementation corrected these defects and improved cognition. This trial suggests that supplementing GlyNAC may be important for improving/preventing age-associated cognitive-decline in older adults.
- Published
- 2020
15. Lactobacillus acidophilus attenuates Aeromonas hydrophila induced cytotoxicity in catla thymus macrophages by modulating oxidative stress and inflammation
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Madhubanti Basu, Mrinal Samanta, Surajit Das, Premranjan Kumar, Rajanya Banerjee, Arttatrana Pal, and Bhakti Patel
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0301 basic medicine ,Carps ,DNA damage ,medicine.medical_treatment ,Immunology ,Apoptosis ,Aquaculture ,medicine.disease_cause ,Polymerase Chain Reaction ,Microbiology ,Fish Diseases ,03 medical and health sciences ,chemistry.chemical_compound ,Lactobacillus acidophilus ,medicine ,Animals ,Molecular Biology ,Reactive nitrogen species ,Inflammation ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Macrophages ,Probiotics ,Flow Cytometry ,biology.organism_classification ,Catla ,Aeromonas hydrophila ,Oxidative Stress ,030104 developmental biology ,Cytokine ,chemistry ,Comet Assay ,Gram-Negative Bacterial Infections ,Oxidative stress - Abstract
The pathogenesis of Aeromonas hydrophila, a potent fish pathogen, is attributed to its ability to cause motile aeromonad septicaemia leading to apoptosis in a myriad of fish species, including freshwater carp Catla catla. However, the underlying mechanism of antagonistic activity of probiotics against A. hydrophila induced apoptosis is not elucidated due to lack of appropriate in-vitro models. This study reported that the exposure of catla thymus macrophages (CTM) to A. hydrophila markedly induced cellular injuries as evidenced by elevated levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), increased apoptosis, DNA damage and decreased cellular viability. Flow cytometry analysis and Annexin-V/propidium iodide assay further confirmed increased ROS positive cells leading to cell death after infection. The quantitative real-time PCR analysis, also revealed upregulation of inducible nitric-oxide synthase (iNOS), pro-inflammatory cytokine (TNFα), cyclooxygenase2 (COX-2) and downregulation of anti-inflammatory cytokine (IL-10). Pretreatment of cells with probiotic, Lactobacillus acidophilus attenuated A. hydrophila induced apoptosis as evident from the decrease in the levels of ROS, RNS and DNA damage. Significant increase (P≤0.05) in expression of TNFα and IL-10 and decrease in iNOS and COX-2 was observed on probiotic stimulation. In-vivo study using catla fingerlings confirmed similar pattern of ROS, iNOS, NO production and cytokine expression in thymus. This study provides a comprehensive insight into the mechanistic basis of L. acidophilus induced macrophage mediated inflammatory response against A. hydrophila in CTM cells. Further, it speculates the possibility of using cost-effective in-vitro models for screening probiotic candidates of therapeutic potential in aquaculture industry.
- Published
- 2016
16. CORRECTING GLUTATHIONE DEFICIENCY REVERSES MITOCHONDRIAL DYSFUNCTION AND ACCELERATED AGING IN PATIENTS WITH HIV
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Chun Liu, James W. Suliburk, Rajagopal V. Sekhar, Charles G. Minard, and Premranjan Kumar
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medicine.medical_specialty ,Health (social science) ,business.industry ,Human immunodeficiency virus (HIV) ,medicine.disease_cause ,Health Professions (miscellaneous) ,Accelerated aging ,Session 2485 (Symposium) ,Abstracts ,Endocrinology ,Internal medicine ,Glutathione deficiency ,medicine ,In patient ,Life-span and Life-course Studies ,business - Abstract
Patients with HIV (PWH) have ‘accelerated’ aging based on early manifestation of geriatric comorbidities of declining physical-function, elevated inflammation, insulin-resistance, cognitive-impairment and abdominal-obesity, but contributing mechanisms are not well understood and interventions are lacking. We hypothesized that deficiency of the intracellular-antioxidant Glutathione results in impaired mitochondrial fuel-oxidation (MFO) and contributes to these defects, and that supplementing Glutathione precursors glycine and N-acetylcysteine (GlyNAC) could improve these defects. In an open-label trial, 8 PWH were studied before and after 12-weeks of GlyNAC supplementation (and 8-weeks after stopping GlyNAC), and compared to 8 matched, unsupplemented, uninfected controls. PWH had significantly impaired MFO, abnormal molecular regulation of MFO, muscle Glutathione deficiency, physical decline, cognitive-impairment, and higher oxidative-stress, inflammation, insulin-resistance and total body fat. GlyNAC supplementation significantly improved these defects, but benefits receded on stopping GlyNAC. These data suggest that GlyNAC supplementation could reverse ‘accelerated aging’ in PWH by improving defects linked to impaired MFO.
- Published
- 2019
17. GLUTATHIONE, MITOCHONDRIAL DEFECTS, AND A UNIQUE METABOLIC CYCLE IN OLDER HUMANS: IMPLICATIONS FOR SARCOPENIA
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Chun Liu, Farook Jahoor, Premranjan Kumar, Shaji Chacko, Jean Hsu, and Rajagopal V. Sekhar
- Subjects
medicine.medical_specialty ,Health (social science) ,business.industry ,Glutathione ,medicine.disease ,Health Professions (miscellaneous) ,chemistry.chemical_compound ,Abstracts ,Endocrinology ,Biology of Aging ,chemistry ,Sarcopenia ,Internal medicine ,medicine ,Life-span and Life-course Studies ,business ,Session 1310 (Poster) - Abstract
Sarcopenia in aging leads to decreased muscle mass and physical-function (muscle strength and exercise capacity), but underlying mechanisms are not well understood and effective interventions are limited. We hypothesized that deficiency of the intracellular antioxidant protein Glutathione initiates a unique self-perpetuating metabolic cycle linking impaired fasted mitochondrial fuel-oxidation (fMFO) to protein catabolism and contributes to sarcopenia. We also hypothesized that supplementing the Glutathione precursor amino-acids glycine and N-acetylcysteine (GlyNAC) to correct Glutathione deficiency in older humans could reverse these defects. We tested our hypothesis in a 24-week open-label clinical-trial in 8 older-humans (74y) studied before and 24-weeks after GlyNAC supplementation, compared to 8 gender-matched unsupplemented young-controls (25y), and measured intracellular Glutathione concentrations, fMFO, physical-function, muscle-protein breakdown-rate (MPBR), gluconeogenesis, and urine nitrogen-excretion (UNE). GlyNAC supplementation in older humans corrected Glutathione deficiency and restored impaired fMFO (to levels in young controls), lowered MPBR and UNE, and increased physical-function, but did not affect gluconeogenesis or increase lean-mass, and suggest that muscle amino-acids are utilized for energy needs rather than glucose production. The absence of an increase in lean-mass suggests that GlyNAC should be combined with anabolic agents for potential benefits in combating sarcopenia. Overall, these results indicate the presence of a unique reversible metabolic cycle in older humans initiated by Glutathione deficiency which results in impaired mitochondrial fatty-acid and glucose oxidation, muscle-protein breakdown, UNE, and leads to deficiency of glycine and cysteine which re-initiate the cycle. These data have implications for improving physical-function and muscle mass in age-associated sarcopenia, and warrants further investigation.
- Published
- 2019
18. CORRECTING GLUTATHIONE DEFICIENCY AND MITOCHONDRIAL DYSFUNCTION IN OLDER HUMANS: A RANDOMIZED CLINICAL TRIAL
- Author
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Farook Jahoor, George E. Taffet, Jean W. Hsu, James W. Suliburk, Rajagopal V. Sekhar, Charles G. Minard, Chun Liu, and Premranjan Kumar
- Subjects
medicine.medical_specialty ,Health (social science) ,business.industry ,Health Professions (miscellaneous) ,law.invention ,Abstracts ,Randomized controlled trial ,law ,Internal medicine ,Glutathione deficiency ,medicine ,Session 2190 (Symposium) ,Life-span and Life-course Studies ,business - Abstract
Aging is associated with impaired mitochondrial fatty-acid oxidation (MFO) due to unknown mechanisms, and interventions are lacking. We hypothesized that impaired MFO in aging occurs due to Glutathione-deficiency and tested this in a randomized, placebo-controlled double-blind clinical-trial in 24 older-humans (71.1y) and 12 young-controls (25.5y) using calorimetry, muscle-biopsy and tracer-protocols. Older-humans received either GlyNAC (Glycine 1.33mmol/kg/d and N-acetylcysteine 0.83mmol/kg/d as Glutathione precursors) or isonitrogenous-placebo for 16-weeks; young-controls received GlyNAC for 2-weeks. Compared to young-controls, older humans had significantly lower Glutathione, impaired MFO, lower gait-speed and physical-function, and higher oxidative-stress, inflammation and insulin-resistance. GlyNAC supplementation in older-humans significantly improved and restored MFO; increased gait-speed (19%,) and physical-function; and decreased oxidative-stress (TBARS 80%), inflammation (IL-6 83%; TNF-alpha 58%), and insulin-resistance (HOMA-IR 68%), but young-controls were unaffected. These data provide proof-of-concept that GlyNAC supplementation could improve the health of older-humans by correcting Glutathione-deficiency and mitochondrial-defects to improve gait-speed, oxidative-stress, inflammation and insulin-resistance.
- Published
- 2019
19. Tyrosine kinase in ulcerative colitis associated compromised microglial functions
- Author
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Jayshree Mishra, Narendra Kumar, and Premranjan Kumar
- Subjects
business.industry ,Genetics ,medicine ,Cancer research ,medicine.disease ,business ,Molecular Biology ,Biochemistry ,Ulcerative colitis ,Tyrosine kinase ,Biotechnology - Published
- 2018
20. Effects of CEES and LPS synergistically stimulate oxidative stress inactivates OGG1 signaling in macrophage cells
- Author
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Premranjan Kumar, Reena Rani Behera, Arttatrana Pal, and Satish Sagar
- Subjects
Lipopolysaccharides ,Environmental Engineering ,Lipopolysaccharide ,Cell Survival ,Health, Toxicology and Mutagenesis ,Apoptosis ,Biology ,medicine.disease_cause ,Cell Line ,DNA Glycosylases ,Mice ,chemistry.chemical_compound ,Downregulation and upregulation ,Mustard Gas ,Tuberous Sclerosis Complex 2 Protein ,medicine ,Animals ,Environmental Chemistry ,Chemical Warfare Agents ,Viability assay ,Waste Management and Disposal ,Protein kinase B ,Superoxide Dismutase ,Macrophages ,Tumor Suppressor Proteins ,Cell Cycle ,Deoxyguanosine ,Catalase ,Reactive Nitrogen Species ,Pollution ,Cell biology ,Oxidative Stress ,chemistry ,8-Hydroxy-2'-Deoxyguanosine ,Phosphorylation ,Mitogen-Activated Protein Kinases ,Signal transduction ,Reactive Oxygen Species ,hormones, hormone substitutes, and hormone antagonists ,Intracellular ,Oxidative stress ,DNA Damage - Abstract
2-chloroethyl ethyl sulphide (CEES), a monofunctional analogue of sulfur mustard, is a strong vesicant and an alkylating chemical warfare agent. We studied the molecular mechanism of oxidative stress triggered signaling cascades in murine macrophages exposed to CEES with lipopolysaccharide (LPS). Exposure of CEES with specific dose of LPS stimulates oxidative stress caused increasing level of intracellular ROS and RNS, decreased antioxidant enzymes, increasing bimolecular damage, reduced cell viability, and cell cycle arrest. Synergistic exposure of CEES and LPS provoked significant increase in phosphorylation of MAPKs, Akt, tuberin, that down regulate OGG1 expression and 8-OHdG accumulations. Treatment with Akt and ERK1/2 inhibitors, the cells with constitutively active inhibiting activity of Akt and ERK1/2MAPK significant reduce CEES and LPS challenge tuberin but not the OGG1. In addition, the N-acetylcysteine inhibited ROS/RNS generation, elevation of antioxidants level, expression of ERK1/2, Akt, tuberin phosphorylation, resulted in deceased 8-OHdG accumulation and upregulation of OGG1 protein expression suggesting no involvement of Akt and ERK1/2MAPK pathways after CEES and LPS challenge. Collectively, our results indicate that exposure of CEES and LPS induces oxidative stress and the activation of tuberin, and 8-OHdG accumulation via upstream signaling pathways including Akt and ERK1/2MAPK pathway in macrophages but not the down regulation of OGG1.
- Published
- 2014
21. Hyperglycemia-induced oxidative stress induces apoptosis by inhibiting PI3-kinase/Akt and ERK1/2 MAPK mediated signaling pathway causing downregulation of 8-oxoG-DNA glycosylase levels in glial cells
- Author
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Premranjan Kumar, Arttatrana Pal, G Nageswar Rao, and Bibhuti Bhusan Pal
- Subjects
Apoptosis ,Oxidative phosphorylation ,Biology ,medicine.disease_cause ,Biochemistry ,DNA Glycosylases ,Phosphatidylinositol 3-Kinases ,Diabetic Neuropathies ,Downregulation and upregulation ,medicine ,Animals ,Humans ,Cysteine ,Protein kinase B ,Mitogen-Activated Protein Kinase Kinases ,Kinase ,Cell Biology ,Cell cycle ,Rats ,Cell biology ,Oncogene Protein v-akt ,Oxidative Stress ,Glucose ,Hyperglycemia ,Phosphorylation ,Lipid Peroxidation ,Signal transduction ,Neuroglia ,Oxidative stress ,Signal Transduction - Abstract
Glial cells are very important for normal brain function and alterations in their activity due to hyperglycemia, could contribute to diabetes-related cognitive dysfunction. Oxidative insults often cause rapid changes in almost all cells including glial cells. However, pathophysiologic mechanisms that lead to diabetic complications are not completely elucidated. Therefore, we examined whether elevated glucose levels directly or indirectly disrupt antioxidant defense mechanisms causing alterations in signaling pathways, cell cycle dysregulation, and reactive oxygen/nitrogen species-mediated apoptosis in glial cells. Findings of this study demonstrated that exposure of glial cells to high glucose markedly induces cellular and molecular injuries, as evidenced by elevated levels of reactive oxygen/nitrogen species, biomolecules damage, cell cycle dysregulation, decrease in antioxidant enzymes, and decrease in cell viability. Pretreatment of cells with N-acetyl-L-cysteine reduced high glucose-induced cytotoxicity by increasing the levels of antioxidant enzymes, and decreasing the number of apoptotic cells. Further, at molecular level high glucose treatment resulted in a significant increase in phosphorylation of Akt, MAPKs, tuberin, down regulation of 8-oxoG-DNA glycosylase and increase in 8-hydroxydeoxyguanosine accumulations. Pretreatment of cells with N-acetyl-L-cysteine, phosphatidylinositol3-kinase/Akt and ERK1/2 inhibitors completely abolished the apoptotic effects of high glucose. Moreover, N-acetyl-L-cysteine significantly inhibited reactive oxygen/nitrogen species generation, elevated antioxidants levels, inhibited Akt, ERK1/2, tuberin phosphorylation, decreased 8-hydroxydeoxyguanosine accumulation and upregulated 8-oxoG-DNA glycosylase expression. Our results demonstrate that high glucose induces apoptosis and inhibits proliferation of glial cells, which may be mediated by the phosphorylation of tuberin, down regulation of 8-oxoG-DNA glycosylase and 8-hydroxydeoxyguanosine accumulation via activation of Akt and ERK1/2MAPK pathways.
- Published
- 2014
22. Hyperglycemia-induced inflammation caused down-regulation of 8-oxoG-DNA glycosylase levels in murine macrophages is mediated by oxidative-nitrosative stress-dependent pathways
- Author
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Mitali Madhusmita Swain, Arttatrana Pal, and Premranjan Kumar
- Subjects
0301 basic medicine ,Chemokine ,Inflammation ,medicine.disease_cause ,Biochemistry ,Proinflammatory cytokine ,DNA Glycosylases ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Downregulation and upregulation ,medicine ,Animals ,Protein kinase B ,Reactive nitrogen species ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Macrophages ,Cell Biology ,Reactive Nitrogen Species ,Cell biology ,Oxidative Stress ,030104 developmental biology ,Glucose ,chemistry ,Hyperglycemia ,biology.protein ,medicine.symptom ,Oxidation-Reduction ,Oxidative stress ,Signal Transduction - Abstract
High glucose-induced increase in production of reactive oxygen/nitrogen species (ROS/RNS) is recognized as a major cause of the clinical complications associated with diabetes. ROS/RNS apart from being redox agents, cause an unwanted severe physiological load to cells, also act as cellular messengers, and play a key role in activation of circulating macrophages. However, the molecular mechanisms of activation of macrophages by hyperglycemic conditions are currently unclear. In the present study, we report that high glucose (HG) causes a dramatic increase in the production of inflammatory cytokines and chemokines, at least in part through enhanced mRNA transcription. The increase in levels of inflammatory cytokines/chemokines corresponds to increased levels of ROS/RNS, which is accompanied by increased activities of Akt, ERK1/2, tuberin, down regulation of 8-oxoG-DNA glycosylase (OGG1), and increase in 8-hydroxydeoxyguanosine (8-OHdG) accumulation in DNA. Elevated levels of ROS/RNS are triggering alteration in antioxidants level, biomolecules damage, cell cycle dysregulation, and apoptosis in macrophage cells. Pretreatment of antioxidants caused decrease in the levels of ROS/RNS leads to an increase in the levels of antioxidants, decrease in biomolecules damage, alterations in Akt, ERK1/2, tuberin, upregulation of OGG1, and decrease in 8-OHdG accumulations in DNA. Further, antioxidants treatments inhibit the effects of HG on the transcriptional activity of cytokines and chemokines. Our results demonstrate that intracellular signaling pathways mediated by ROS/RNS are linked to each other by elevated glucose in macrophages activation leading to inflammation. These findings provide a mechanistic explanation of how ROS/RNS cooperate to conduct inflammatory intracellular signals in macrophages related complications in hyperglycemic conditions.
- Published
- 2015
23. Hyperglycemia-Induced Oxidative-Nitrosative Stress Induces Inflammation and Neurodegeneration via Augmented Tuberous Sclerosis Complex-2 (TSC-2) Activation in Neuronal Cells
- Author
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Premranjan Kumar, Rangnath Mishra, Arttatrana Pal, Thiagarajan Raman, and Mitali Madhusmita Swain
- Subjects
0301 basic medicine ,Male ,Nitrosation ,Neuroscience (miscellaneous) ,Inflammation ,Biology ,medicine.disease_cause ,PC12 Cells ,Antioxidants ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Downregulation and upregulation ,Tuberous Sclerosis ,Tuberous Sclerosis Complex 2 Protein ,medicine ,Animals ,Rats, Wistar ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cells, Cultured ,Neurons ,Tumor Suppressor Proteins ,Neurodegeneration ,Neurodegenerative Diseases ,medicine.disease ,Cell biology ,Rats ,Oxidative Stress ,030104 developmental biology ,Neurology ,Hyperglycemia ,Immunology ,Phosphorylation ,medicine.symptom ,Inflammation Mediators ,Cell activation ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
Diabetes is a systemic disease mainly characterized by chronic hyperglycemia and with extensive and long-lasting spiteful complications in central nervous systems (CNS). Astrocytes play an important role in the defense mechanism of CNS, with great ability of withstanding accumulation of toxic substances. Apart from functional disorders, hyperglycemia leads to slow progressive structural abnormalities in the CNS through oxidative stress pathways. However, the molecular mechanism by which neurons die under oxidative stress induced by high glucose (HG) remains largely unclear. Here, we report that HG-induced inflammation and neurodegeneration in brain tissues, brain astrocytes (C6), and pheochromocytoma (PC-12) cells are cultured in HG conditions. Our results show that the increases in phosphorylation of Akt and ERK1/2MAPK are associated with increased accumulations of reactive oxygen species (ROS) in neuronal cells, which simultaneously enhanced phosphorylations of tuberous sclerosis complex-2 (TSC-2) and mammalian target of rapamycin (mTOR) in the diabetic brain and in HG-exposed neuronal cells. Pharmacologic inhibition of Akt or ERK1/2 or siRNA-mediated gene silencing of TSC-2 suppressed the strong downregulation of TSC-2-mTOR activation. Findings of this study also demonstrate that HG resulted in phosphorylation of NF-κB, coinciding with the increased production of inflammatory mediators and activation of neurodegenerative markers. Pretreatment of cells with antioxidants, phosphoinositide3-kinase (PI3-K)/Akt, and ERK1/2 inhibitors significantly reduced HG-induced TSC-2 phosphorylation and restored NF-κB protein expression leading to decreased production of inflammatory mediators and neurodegenerative markers. These results illustrate that ROS functions as a key signaling component in the regulatory pathway induced by elevated glucose in neuronal cell activation leading to inflammation and neurodegeneration.
- Published
- 2015
24. Incidence of cystoid macular oedema in diabetic patients after phacoemulsification and free radical link to its pathogenesis
- Author
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Arttatrana Pal, Premranjan Kumar, Sanghamitra Machhua, Anupam Samanta, and G Nageswar Rao
- Subjects
Moderate to severe ,Adult ,Male ,medicine.medical_specialty ,Free Radicals ,medicine.medical_treatment ,education ,Visual Acuity ,Antioxidants ,Macular Edema ,Diabetic nephropathy ,Pathogenesis ,Cellular and Molecular Neuroscience ,Risk Factors ,Ophthalmology ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Aged ,Aged, 80 and over ,Diabetic Retinopathy ,Phacoemulsification ,business.industry ,Incidence (epidemiology) ,Diabetic retinopathy ,Middle Aged ,medicine.disease ,Sensory Systems ,Diabetes Mellitus, Type 2 ,Cystoid macular oedema ,Female ,business ,Reactive Oxygen Species ,Biomarkers - Abstract
Postoperative onset of cystoid macular oedema (CME) in diabetic patients after cataract surgery is a frequent problem in working-age adults worldwide. Here, we investigate the postoperative development of CME in diabetic patients after undergoing phacoemulsification with other ailing factors associated with CME.This prospective study included 65 Type 2 diabetic patients with no diabetic retinopathy (DR), mild to moderate DR, moderate to severe DR and proliferative DR who underwent phacoemulsification surgery. Indirect ophthalmoscopy, fluorescein angiograms and optical coherence tomography were taken for a period of 8 weeks postoperatively to determine visual outcome and development of CME. Serum samples were collected for the measurement of antioxidants and reactive oxygen species (ROS) levels.Our data showed that CME occurred postoperatively in 47% without pre-existing DR and 55% of eyes with pre-existing DR (p005). Positive association was noticed between morbid conditions, like hypertension (p0.01) and diabetic nephropathy (p0.05), and postoperative incidence of CME. The activity of antioxidant enzymes in patients with DR was found to be lower as compared with diabetic (D) patients, but catalase activity was recorded the maximum in these patients. The ROS activity was recorded highest in the serum samples of DR becoming CME positive.The present results suggest that after phacoemulsification, the chance of development of CME in DR is more as compared to D. Moreover, the development of CME is significantly associated with decrease in antioxidant levels, increased ROS activities, hypertension, diabetic nephropathy, and hyperlipidaemia.
- Published
- 2014
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