204 research outputs found
Role of folic acid induced oxidative stress in acute kidney injury and kidney fibrosis
No full textKidneys are vital organs that filter and purify metabolic waste and maintain homeostasis of body fluids for normal physiological function. Kidney disease may affect any age of people, and an estimated 10 % of people worldwide are affected by chronic kidney disease. The only available options for kidney patients with end-stage renal disease are hemodialysis and renal replacement. These options are too costly, and because of that, it is not accessible to all socioeconomic groups. There are no approved therapeutics for reversing kidney injury and kidney fibrosis.
One of the common mechanisms proposed in kidney fibrosis and kidney injury involves oxidative damage to cellular molecules by reactive oxygen species (ROS). Reports show that oxidative stress-induced molecular pathways are induced during the initiation and progression of fibrosis. The folic acid-induced kidney fibrosis mouse model is an established model to study the mechanism of kidney injury and kidney fibrosis. In this study, we uncover how a high dose of folic acid-induced oxidative stress leads to acute kidney injury and the long-term development of kidney fibrosis. C57BL/6 mice were used as an in vivo model, and Caki-1, HK-2 and NRK cells as in vitro models to study high concentrations of folic acid-mediated kidney injury and kidney fibrosis. We assessed in vitro toxicity using the MTT cell viability assay and ROS generation using the DCF assay. The consequences of ROS on the cell cycle were analyzed by Flow cytometry. Further analysis of transcript abundance by qRT - PCR was performed on samples from in vivo exposed mouse kidneys and from in vitro exposed cell lines to confirm the effect of an increased level of ROS on a molecular level.
In this study, we have reported the toxicity of the high concentration of Folic Acid on Kidney epithelial cells via the generation of ROS. Further molecular analysis confirms that the generation of ROS-mediated downstream effects proceeds fibrogenesis via epithelial to mesenchymal transition (EMT) of Renal tubular Epithelial cells.Restricted until 06/2027. To request the author grant access, click on the PDF link to the left
अांबेडकर
No full textA corpus of grindmill songs dedicated to the memory of Bhimrao Ramji Ambedkar (1891-1956) by Mahar women in Maharashtra (India)Un corpus de canciones de la molienda dedicados a la memoria de Bhimrao Ramji Ambedkar (1891-1956) por las mujeres Mahar en Maharashtra (India)Corpus de chants de la mouture par des femmes de caste Mahar au Maharashtra (Inde) à la mémoire de Bhimrao Ramji Ambedkar (1891-1956)महाराष्ट्रातील महार स्त्रियांनी भीमराव रामजी आंबेडकरांच्या स्मृतीस वाहीलेली गाणी (१८९१-१९५६)BEL, B. Le corpus « Ambedkar ». Travaux Interdisciplinaires du Laboratoire Parole et Langage d'Aix-en-Provence (TIPA), no. 25. 2006, p. 19-30.http://hal.archives-ouvertes.fr/hal-0013639
Relation of serial changes in childhood body-mass index to impaired glucose tolerance in young adulthood
No full textBackground: The risk of type 2 diabetes mellitus is increased in people who have low birth weights and who subsequently become obese as adults. Whether their obesity originates in childhood and, if so, at what age are unknown. Understanding the origin of obesity may be especially important in developing countries, where type 2 diabetes is rapidly increasing yet public health messages still focus on reducing childhood "undernutrition."Methods: We evaluated glucose tolerance and plasma insulin concentrations in 1492 men and women 26 to 32 years of age who had been measured at birth and at intervals of three to six months throughout infancy, childhood, and adolescence in a prospective, population-based study.Results: The prevalence of impaired glucose tolerance was 10.8 percent, and that of diabetes was 4.4 percent. Subjects with impaired glucose tolerance or diabetes typically had a low body-mass index up to the age of two years, followed by an early adiposity rebound (the age after infancy when body mass starts to rise) and an accelerated increase in body-mass index until adulthood. However, despite an increase in body-mass index between the ages of 2 and 12 years, none of these subjects were obese at the age of 12 years. The odds ratio for disease associated with an increase in the body-mass index of 1 SD from 2 to 12 years of age was 1.36 (95 percent confidence interval, 1.18 to 1.57; P<0.001).Conclusions: There is an association between thinness in infancy and the presence of impaired glucose tolerance or diabetes in young adulthood. Crossing into higher categories of body-mass index after the age of two years is also associated with these disorders
Role of Nephrotoxicant - Induced Oxidative Stress in Acute Kidney Injury and Kidney Fibrosis
No full textThe kidney is an essential organ that filters metabolic waste from the body and maintains the balance of body fluids necessary for normal functioning. Kidney disease can affect individuals of any age, with an estimated 10% of the global population impacted by chronic kidney disease. Due to the kidney's filtration function, it is exposed to various xenobiotics, including nephrotoxins. Kidney epithelial cells, which play a significant role in filtration and active transport, are particularly vulnerable to exposure to nephrotoxins.
For patients with end-stage renal disease, renal replacement therapies such as hemodialysis are often the only available options. However, these treatments can be invasive and costly, making them inaccessible to individuals across different socioeconomic backgrounds. Unfortunately, there are currently no approved therapeutics for reversing kidney injury or kidney fibrosis. Reactive oxygen species (ROS) are often observed during kidney injury caused by nephrotoxins, and several studies indicate that oxidative stress-induced molecular pathways contribute to the initiation and progression of fibrosis. The folic acid-induced kidney fibrosis mouse model is a well-established model for studying the mechanisms of kidney injury and fibrosis.
In this study, we investigate how exposure to nephrotoxins—specifically high doses of folic acid and arsenic—leads to oxidative stress, resulting in acute kidney injury and the long-term development of kidney fibrosis. We utilized C57BL/6 mice as our in vivo model and Caki-1 and HK-2 epithelial cell lines as our in vitro models to evaluate nephrotoxin-induced kidney injury and fibrosis. The generation of ROS in kidney epithelial cells due to arsenic exposure was measured using the DCF assay. The impact of ROS on DNA damage was assessed through RAPD PCR in kidney epithelial cells. We evaluated the effects of a high dose (125 mg/kg) of folic acid injection on mouse health and kidney function by measuring body weight, serum albumin levels, and creatinine levels. Kidney injury and fibrosis were assessed using histopathological examination and immunofluorescence analysis. We examined the molecular consequences of ROS by analyzing transcript and protein expression through qRT-PCR and Western blotting of RNA and protein isolated from both in vivo mouse kidneys and in vitro cell lines.
The results of this study revealed that nephrotoxins induce ROS production, leading to DNA damage and cytotoxicity in vitro, as well as reduced kidney function in the in vivo mouse model. This response was associated with changes in antioxidant levels, as well as alterations in genes and proteins related to DNA damage. Consequently, fibrogenic genes were activated through specific signaling pathways, including TGF-Beta/Smad, Notch, and Wnt/B-catenin signaling. The underlying molecular mechanisms for these alterations were linked to oxidative stress-induced changes in epigenetic regulatory mechanisms, such as histone modification and DNA methylation.
In summary, our findings indicate that the activation of fibrogenic signaling is reversible by antioxidants, which restore epigenetic regulatory proteins, suggesting that oxidative stress plays a crucial role in fibrogenesis
Molecular basis of resistance in wheat varieties against spot blotch disease
No full textDuring present investigation, among the six wheat genotypes tested against six isolates of Bipolaris sorokiniana, the genotype BOW‘S’ showed resistance response against three isolates, namely, BS-D-1, BS-DWRK-2 and BS-K-4, whereas moderately resistance response against remaining 3 isolates i.e. BS-F-3, BS-P-5 and BS-V-6.The genotype A-9-30-1 showed almost highly susceptible response against each isolate except BS-D-1 which exhibited susceptible reaction on this genotype. Thus, it is clear that genotype BOW ‘S’ has broad genetic base for resistance, whereas genotype A-9-30-1 has no gene for resistance against these six isolates tested. Remaining five genotypes showed varying response, ranging from highly susceptible, susceptible, moderately susceptible, moderately resistant and resistant against various isolates of B. sorokiniana tested
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