ABSTRACT
BACKGROUND: Chrysin, a polyphenolic compound, possesses antioxidant and anti-inflammatory properties. In this study, we investigated the effect of chrysin on the expression of A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), a protease enzyme involved in degrading extracellular matrix associated with atherosclerosis. METHODS AND RESULTS: We have studied the cell viability by MTT assay and foam cell formation by oil red O staining. The mRNA and protein expression of ADAMTS-4 was studied using quantitative polymerase chain reaction (qPCR) and Western blotting, respectively. Our study showed that chrysin significantly downregulates the expression of ADAMTS-4 in foam cells. CONCLUSION: Chrysin's ability to downregulate the expression of ADAMTS-4, a protease involved in degrading the extracellular matrix, bestows upon it a new therapeutic potential for managing atherosclerosis.
Subject(s)
ADAMTS4 Protein , Down-Regulation , Flavonoids , Foam Cells , Flavonoids/pharmacology , ADAMTS4 Protein/metabolism , ADAMTS4 Protein/genetics , Foam Cells/drug effects , Foam Cells/metabolism , Down-Regulation/drug effects , Humans , Cell Survival/drug effects , Atherosclerosis/metabolism , Atherosclerosis/drug therapy , Atherosclerosis/geneticsABSTRACT
The primary objective of forensic investigation of a case is to recognize, identify, locate, and examine the evidence. Microscopy is a technique that provides crucial information for resolving a case or advancing the investigation process by analyzing the evidence obtained from a crime scene. It is often used in conjunction with suitable analytical techniques. Various microscopes are employed; scanning probe microscopes are available in diverse forensic analyses and studies. Among these, the atomic force microscope (AFM) is the most commonly used scanning probe technology, offering a unique morphological and physico-chemical perspective for analyzing multiple pieces of evidence in forensic investigations. Notably, it is a non-destructive technique capable of operating in liquid or air without complex sample preparation. The article delves into a detailed exploration of the applications of AFM in the realms of nanomechanical forensics and nanoscale characterization of forensically significant samples.
Subject(s)
Forensic Sciences , Microscopy, Atomic Force , Humans , Forensic Sciences/methodsABSTRACT
Atherosclerosis is a chronic inflammatory disease forming plaques in medium and large-sized arteries. ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) is an extracellular-matrix remodelling enzyme involved in the degradation of versican in the arterial wall. Recent reports indicated that increased expression of ADAMTS-4 is associated with plaque progression and vulnerability. Bioactive components of dietary oil, like sesame oil, are reported to have anti-inflammatory and antioxidant properties. Here, we studied the effect of sesame oil on regulating ADAMTS-4 in high-fat diet-induced atherosclerosis rat model. Our results indicated that sesame oil supplementation improved the anti-inflammatory and anti-oxidative status of the body. It also reduced atherosclerotic plaque formation in high-fat diet-fed rats. Our results showed that the sesame oil supplementation significantly down-regulated the expression of ADAMTS-4 in serum and aortic samples. The versican, the large proteoglycan substrate of ADAMTS-4 in the aorta, was downregulated to normal control level on sesame oil supplementation. This study, for the first time, reveals that sesame oil could down-regulate the expression of ADAMTS-4 in high-fat diet-induced atherosclerosis, imparting a new therapeutic potential for sesame oil in the management of atherosclerosis.
Subject(s)
ADAMTS4 Protein , Atherosclerosis , Diet, High-Fat , Down-Regulation , Sesame Oil , Animals , Sesame Oil/pharmacology , ADAMTS4 Protein/metabolism , ADAMTS4 Protein/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atherosclerosis/drug therapy , Atherosclerosis/genetics , Diet, High-Fat/adverse effects , Down-Regulation/drug effects , Rats , Male , Versicans/metabolism , Versicans/genetics , Rats, Sprague-Dawley , ADAM Proteins/metabolism , ADAM Proteins/genetics , Aorta/metabolism , Aorta/drug effects , Aorta/pathologyABSTRACT
Cardiac function depends mainly on mitochondrial metabolism. Cold conditions increase the risk of cardiovascular diseases by increasing blood pressure. Adaptive thermogenesis leads to increased mitochondrial biogenesis and function in skeletal muscles and adipocytes. Here, we studied the effect of acute cold exposure on cardiac mitochondrial function and its regulation by sirtuins. Significant increase in mitochondrial DNA copy number as measured by the ratio between mitochondrial-coded COX-II and nuclear-coded cyclophilin A gene expression by qRT-PCR and increase in the expression of PGC-1α, a mitochondriogenic factor and its downstream target NRF-1 were observed on cold exposure. This was associated with an increase in the activity of SIRT-1, which is known to activate PGC-1α. Mitochondrial SIRT-3 was also upregulated. Increase in sirtuin activity was reflected in total protein acetylome, which decreased in cold-exposed cardiac tissue. An increase in mitochondrial MnSOD further indicated enhanced mitochondrial function. Further evidence for this was obtained from ex vivo studies of cardiac tissue treated with norepinephrine, which caused a significant increase in mitochondrial MnSOD and SIRT-3. SIRT-3 appears to mediate the regulation of MnSOD, as treatment with AGK-7, a SIRT-3 inhibitor reversed the norepinephrine-induced upregulation of MnSOD. It, therefore, appears that SIRT-3 activation in response to SIRT-1-PGC-1α activation contributes to the regulation of cardiac mitochondrial activity during acute cold exposure.