The tumor micro-environment is a key determinant for promoting cancer cell growth and development with exosomal miRNAs emerging as key regulators of tumor growth and metastasis. miR16 is one well-established tumor suppressor miRNAs that induces apoptosis, while inhibiting angiogenesis and inflammation across various cancers. Herein, we investigated the role of exosomal miR16 in the cervical cancer microenvironment and its underlying molecular mechanisms.
View Article and Find Full Text PDFInflammation in macrophages is exacerbated under hyperglycemic conditions, contributing to chronic inflammation and impaired wound healing in diabetes. This study investigates the potential of mangiferin, a natural polyphenol, to alleviate this inflammatory response by targeting a redox-sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2). Mangiferin, a known Nrf2 activator, was evaluated for its ability to counteract the hyperglycemia-induced inhibition of Nrf2 and enhance antioxidant defenses.
View Article and Find Full Text PDFEnviron Toxicol Pharmacol
October 2024
Phthalate-based polymeric plasticizers are widely used for their durability, transparency, and odorless nature, resulting in human exposure through inhalation, ingestion, or contaminated water. Epidemiological studies have identified bis-phthalate as a potential cardiovascular disease risk factor, though its mechanisms remain unclear. This study investigates the effects of bis-phthalate on endothelial dysfunction (ED), an early event in cardiovascular complications, with a focus on Endoplasmic Reticulum (ER) stress pathways.
View Article and Find Full Text PDFNuclear factor E2-related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates proangiogenic mediators, and antioxidant and detoxification enzymes. However, hitherto its regulation in the progression of DFU was poorly examined. The regulation of Nrf2 has been reported to be affected by various factors, including histone deacetylase (HDACs) and DNA methylation.
View Article and Find Full Text PDFNon-healing lesions in diabetic foot ulcers are a significant effect of poor angiogenesis. Epigenetic regulators, mainly lncRNA and miRNA, are recognized for their important roles in disease progression. We deciphered the regulation of lncRNA NEAT1 through the miR-146a-5p/mafG axis in the progression of DFU.
View Article and Find Full Text PDFVitamin D deficiency is prevalent in pregnancy and has been associated with increased occurrences of preeclampsia, cesarean delivery, neonatal bacterial vaginosis, and gestational diabetes. CYP24A1, recognized as a key factor in vitamin D metabolism homeostasis, encodes 24-hydroxylase responsible for converting 25(OH)D3 and 1,25(OH)2D3 into inactive metabolites. Recently, we have reported CYP24A1 overexpression in patients with gestational diabetes mellitus (GDM) and trophoblast cells exposed to hyperglycemia.
View Article and Find Full Text PDFNuclear factor erythroid-2-related factor 2 () is a stress-activated transcription factor regulating antioxidant genes, and a deficiency thereof, slowing lymphangiogenesis, has been reported in diabetic foot ulcer (DFU). The mode of regulation in DFU has been less explored. Emerging studies on miRNA-mediated target regulation show miRNA to be the leading player in the pathogenesis of the disease.
View Article and Find Full Text PDFTranscription factors regulate gene expression and play crucial roles in development and differentiation of pancreatic β-cell. The expression and/or activities of these transcription factors are reduced when β-cells are chronically exposed to hyperglycemia, which results in loss of β-cell function. Optimal expression of such transcription factors is required to maintain normal pancreatic development and β-cell function.
View Article and Find Full Text PDFThe regulation of angiogenesis by nuclear factor erythroid 2-related factor 2 (Nrf2), a master redox transcription factor, is well established. In the present study, we aimed to activate Nrf2 by mangiferin (MG) and investigate its potential to regulate angiogenesis under a hyperglycemic (HG) environment in human endothelial cells. The mRNA expression of Nrf2 and its downstream targets HO-1, SOD-1, and CAT were observed to be decreased at 72 h of HG (33.
View Article and Find Full Text PDFCircular RNA (circRNA) is a neoteric researched transcript that involves gene regulation by serving as a micro-RNA (miRNA) sponge. This circRNA-miRNA-mRNA interaction is being recently explored, and its dysregulation is associated with disease pathogenesis and progression. Studies have demonstrated the involvement of this regulatory network in endothelium dysfunction-mediated regulation of pathology in vascular diseases.
View Article and Find Full Text PDFChronic hyperglycemia damages the nerves and blood vessels, culminating in other vascular complications. Such complications enhance cytokine, oxidative and endoplasmic reticulum (ER) stress. ER is the primary organelle where proteins are synthesised and attains confirmatory changes before its site of destination.
View Article and Find Full Text PDFVitamin D is an essential vitamin indispensable for calcium and phosphate metabolism, and its deficiency has been implicated in several extra-skeletal pathologies, including cancer and chronic kidney disease. Synthesized endogenously in the layers of the skin by the action of UV-B radiation, the vitamin maintains the integrity of the bones, teeth, and muscles and is involved in cell proliferation, differentiation, and immunity. The deficiency of Vit-D is increasing at an alarming rate, with nearly 32% of children and adults being either deficient or having insufficient levels.
View Article and Find Full Text PDFMol Ther Nucleic Acids
December 2021
The majority of the non-protein-coding RNAs are being identified with diversified functions that participate in cellular homeostasis. The circular RNAs (circRNAs) are emerging as noncoding transcripts with a key role in the initiation and development of many physiological and pathological conditions. The advancements in high-throughput RNA sequencing and bioinformatics tools help us to identify several circRNA regulatory pathways, one of which is microRNA (miRNA)-mediated regulation.
View Article and Find Full Text PDFBiomed Pharmacother
January 2022
Long non-coding RNAs (lncRNAs) are the novel class of transcripts involved in transcriptional, post-transcriptional, translational, and post-translational regulation of physiology and the pathology of diseases. Studies have evidenced that the impairment of endothelium is a critical event in the pathogenesis of atherosclerosis and its complications. Endothelial dysfunction is characterized by an imbalance in vasodilation and vasoconstriction, oxidative stress, proinflammatory factors, and nitric oxide bioavailability.
View Article and Find Full Text PDFBackground: Nuclear factor erythroid 2-related factor (Nrf2), a stress-activated transcription factor, has been documented to induce a defense mechanism against oxidative stress damage, and growing evidence considers this signaling pathway a key pharmacological target for the treatment of liver diseases.
Purpose: The present review highlights the role of phytochemical compounds in activating Nrf2 and mitigate toxicant-induced stress on liver injury.
Methods: A comprehensive search of published articles was carried out to focus on original publications related to Nrf2 activators against liver disease using various literature databases, including the scientific Databases of Science Direct, Web of Science, Pubmed, Google, EMBASE, and Scientific Information (SID).
Pharmacol Res
November 2021
Adipose tissue is instrumental in maintaining metabolic homeostasis by regulating energy storage in the form of triglycerides. In the case of over-nutrition, adipocytes favorably regulate lipogenesis over lipolysis and accumulate excess triglycerides, resulting in increased adipose tissue mass. An abnormal increase in hypertrophic adipocytes is associated with chronic complications such as insulin resistance, obesity, diabetes, atherosclerosis and nonalcoholic fatty liver disease.
View Article and Find Full Text PDFStudies have identified dysregulated long non-coding RNA (lncRNA) in several diseases at transcriptional, translational, and post-translational levels. Although our mechanistic knowledge on the regulation of lncRNAs is still limited, one of the mechanisms of action attributed is binding and regulating transcription factors, thus controlling gene expression and protein function. One such transcription factor is nuclear factor erythroid 2-related factor 2 (Nrf2), which plays a critical biological role in maintaining cellular homeostasis at multiple levels in physiological and pathophysiological conditions.
View Article and Find Full Text PDFBackground: The pivotal role of Nuclear factor erythroid-2-related factor 2 (NRF2) in redox homeostasis and wound healing has been well documented. However, the genetic mechanisms that regulate NRF2 in type 2 diabetes and diabetic foot ulcers remain unexplored. The present study investigated the association of single nucleotide polymorphism rs182428269 (-127 C/T) in subjects with type 2 diabetes and diabetic foot ulcers.
View Article and Find Full Text PDFDiabetic non healing wounds often result in significant morbidity and mortality. The number of effective targets to detect these wounds are meagre. Slow lymphangiogenesis is one of the complex processes involved in impaired healing of wounds.
View Article and Find Full Text PDFEndothelial dysfunction (ED) is a key event in the onset and progression of vascular complications associated with diabetes. Regulation of endothelial function and the underlying signaling mechanisms in the progression of diabetes-induced vascular complications have been well established. Recent studies indicate that increased oxidative stress is an important determinant of endothelial injury and patients with hypertension display ED mediated by impaired Nitric Oxide (NO) availability.
View Article and Find Full Text PDFDiabetic Foot Ulcer (DFU) is the most common in patients who have diabetic peripheral neuropathy and angiopathy as well as a foot deformity. The delayed process of wound healing in diabetic condition is mainly due to reduced expression of the growth factors, persistent inflammatory response and endothelial dysfunction. Emerging evidence indicate that miRNAs play a crucial role in regulating angiogenesis, collectively called as "angiomiRs".
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