ABSTRACT
Moderate levels of endogenous reactive oxygen species (ROS) are important for various cellular activities, but high levels lead to toxicity and are associated with various diseases. Levels of ROS are maintained as a balance between oxidants and antioxidants. Accumulating data suggest that oxidative stress is a major factor in deterioration of renal function. In this review, we highlight the possible mechanism by which oxidative stress can lead to chronic kidney disease (CKD). This review also describes therapies that counter the effect of oxidative stress in CKD patients. Numerous factors such as upregulation of genes involved in oxidative phosphorylation and ROS generation, chronic inflammation, vitamin D deficiency, and a compromised antioxidant defense mechanism system cause progressive detrimental effects on renal function that eventually lead to loss of kidney function. Patients with renal dysfunction are highly susceptible to oxidative stress, as risk factors such as diabetes, renal hypertension, dietary restrictions, hemodialysis, and old age predispose them to increased levels of ROS. Biomolecular adducts (DNA, proteins, and lipids) formed due to reaction with ROS can be used to determine oxidative stress levels. Based on the strong correlation between oxidative stress and CKD, reversal of oxidative stress is being explored as a major therapeutic option. Xanthine oxidase inhibitors, dietary antioxidants, and other agents that scavenge free radicals are gaining interest as treatment modalities in CKD patients.
ABSTRACT
Moderate levels of endogenous reactive oxygen species (ROS) are important for various cellular activities, but high levels lead to toxicity and are associated with various diseases. Levels of ROS are maintained as a balance between oxidants and antioxidants. Accumulating data suggest that oxidative stress is a major factor in deterioration of renal function. In this review, we highlight the possible mechanism by which oxidative stress can lead to chronic kidney disease (CKD). This review also describes therapies that counter the effect of oxidative stress in CKD patients. Numerous factors such as upregulation of genes involved in oxidative phosphorylation and ROS generation, chronic inflammation, vitamin D deficiency, and a compromised antioxidant defense mechanism system cause progressive detrimental effects on renal function that eventually lead to loss of kidney function. Patients with renal dysfunction are highly susceptible to oxidative stress, as risk factors such as diabetes, renal hypertension, dietary restrictions, hemodialysis, and old age predispose them to increased levels of ROS. Biomolecular adducts (DNA, proteins, and lipids) formed due to reaction with ROS can be used to determine oxidative stress levels. Based on the strong correlation between oxidative stress and CKD, reversal of oxidative stress is being explored as a major therapeutic option. Xanthine oxidase inhibitors, dietary antioxidants, and other agents that scavenge free radicals are gaining interest as treatment modalities in CKD patients.
ABSTRACT
Till date the comprehensive clinical pictures, comorbid conditions, and long-term complications of COVID-19 are not known. Recently using a multi-omics-based strategy, we have predicted the drugs for COVID-19 management with [~]70% accuracy. Here, using a similar multi-omics-based bioinformatics approach and three-ways of analysis, we identified the symptoms, comorbid conditions, and short, mid and possible long-term complications of COVID-19 with [~]90% precision. In our analysis (i) we identified 27 parent, 170 child, and 403 specific conditions associated with COVID-19. (ii) Among the specific conditions, 36 are viral and 53 short-term, 62 short to mid to long-term, 194 mid to long-term, and 57 are congenital conditions. (iii) At a cut off "count of occurrence" of 4, we found [~] 90% of the enriched conditions are associated with COVID-19. (iv) Except the dry cough and loss of taste, all other COVID-19 associated mild and severe symptoms are enriched. (v) Cardiovascular, pulmonary, metabolic, musculoskeletal, neuropsychiatric, kidney, liver, and immune system disorders are found as top comorbid conditions. (vi) Specific diseases such as myocardial infarction, hypertension, COPD, lung injury, diabetes, cirrhosis, mood disorders, dementia, macular degeneration, chronic kidney disease, lupus, arthritis etc. along with several other diseases are also enriched as top candidates. (vii) Interestingly, many cancers and congenital disorders associated with COVID-19 severity are also identified. (viii) Arthritis, dermatomyositis, glioma, diabetes, psychiatric disorder, cardiovascular diseases having bidirectional relationship with COVID-19 are also found as top ranked conditions. Based on the accuracy ([~]90%) of this analysis, long presence of SARS-CoV-2 RNA in human, and our previously proposed "genetic remittance" assumption, we hypothesize that all the identified comorbid conditions including the short-long-mid and mid-long non-communicable diseases (NCDs) could also be long-term consequences in COVID-19 survivors and warrants long-term observational studies.
ABSTRACT
Background & Objective: Transthyretin (TTR) has been associated with spinocerebellar ataxia (SCA) by several independent case reports. Coexistence of TTR and SCA mutations, overlapping clinical symptoms as well as altered levels of TTR in SCA patients suggest a correlation between TTR and SCA. To our knowledge, no large cohort based study has been attempted to examine the association of SCA with polymorphism in TTR gene. Here, we chose to investigate TTR variations in SCA patients (n=266) and controls (n=192) of North Indian ethnicity. Methods: We sequenced the exons including exon-intron boundaries of TTR gene in 55 patients and 55 controls. We observed four variations which were further genotyped by single base extension method (SNaPshot) in a larger cohort (SCA patients n=211 and controls n=137). Results: A novel synonymous variation c.372 C>G in exon 4 was detected in heterozygous condition in one control sample. We found nominal association for rs1800458 (Gly6Ser), with SCA (p-value < 0.05) which did not remain after Bonferroni correction for multiple tests. Pairwise linkage disequilibrium (LD) analysis revealed no LD between studied SNPs. Further, we employed two-marker sliding window analysis and observed a weak association of haplotype AT of rs1800458 and rs1667251 with SCA patients (p-value <0.05) which was not retained after Bonferroni correction. Conclusion: Our data suggests no association of genetic variations of TTR in SCA pathology.