This article is available online at http://www.jlr.org functions, in addition to structural roles ( 1 ); consequently lipidomic studies have become fundamental for understanding their contribution to health and disease. Mass spectrometry (MS), with its capability of providing structural information, has been the main method of choice in lipidomic studies. Recent technological advances in mass spectrometers, including increased sensitivity, higher mass accuracy, higher scan speeds, and the ability to acquire in both positive and negative mode in one run have resulted in the increased popularity of MS as a detection technique for biomolecules in recent years. This has enabled the mapping of lipids present in fl uids and cells, leading to better understanding of the role of the different lipid classes in the pathophysiology of diseases.A critical step in lipidomic analysis is lipid extraction with an appropriate organic solvent mixture (solvent system) prior to MS detection. The solvent system should be capable of effectively extracting lipids representative of the sample under study without bias, inducing or promoting the degradation of lipids, or introducing contamination by nonlipid components such as sugars, peptides, and amino acids. Therefore, the success in the identifi cation and profi ling of lipids is critically dependent on the efficiency of the extraction step. The performance of the lipid extraction for a given sample (tissue, cell, or fl uid) with a particular solvent system depends on the partitioning of the
Lipid peroxidation products like malondialdehyde, 4-hydroxynonenal and F 2 -isoprostanes are widely used as markers of oxidative stress in vitro and in vivo . This study reports the results of a multi-laboratory validation study by COST Action B35 to assess inter-laboratory and intra-laboratory variation in the measurement of lipid peroxidation. Human plasma samples were exposed to UVA irradiation at different doses (0, 15 J, 20 J), encoded and shipped to 15 laboratories, where analyses of malondialdehyde, 4-hydroxynonenal and isoprostanes were conducted. The results demonstrate a low within-day-variation and a good correlation of results observed on two different days. However, high coeffi cients of variation were observed between the laboratories. Malondialdehyde determined by HPLC was found to be the most sensitive and reproducible lipid peroxidation product in plasma upon UVA treatment. It is concluded that measurement of malondialdehyde by HPLC has good analytical validity for inter-laboratory studies on lipid peroxidation in human EDTA-plasma samples, although it is acknowledged that this may not translate to biological validity.
Increased exposure to nicotine contributes to the development of cardiac dysfunction by promoting oxidative stress, fibrosis, and inflammation. These deleterious events altogether render cardiac myocytes more susceptible to acute cardiac insults such as ischemia-reperfusion (I/R) injury. This study sought to elucidate the role of angiotensin II type I (AT1) receptors in cardiac injury resulting from prolonged nicotine administration in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg ip) for 28 days to induce cardiac dysfunction, alone or in combination with the AT1 receptor antagonist, irbesartan (10 mg/kg, po). Vehicle-treated rats were used as controls. Rat hearts isolated from each experimental group at study endpoint were examined for changes in function, histology, gene expression, and susceptibility against acute I/R injury determined ex vivo. Rats administered nicotine alone exhibited significantly increased cardiac expression of angiotensin II and angiotensin-converting enzyme (ACE) in addition to elevated systolic blood pressure (SBP) and heart rate. Furthermore, nicotine administration markedly reduced left ventricular (LV) performance with concomitant increases in myocardial oxidative stress, fibrosis, and inflammation. Concomitant treatment with irbesartan attenuated these effects, lowering blood pressure, heart rate, oxidative stress, and expression of fibrotic and inflammatory genes. Importantly, the irbesartan-treated group also manifested reduced susceptibility to I/R injury ex vivo. These findings suggest that AT1 receptors play an important role in nicotine-induced cardiac dysfunction, and pharmacological approaches targeting cardiac AT1 receptors may thus benefit patients with sustained exposure to nicotine.
These observations indicate the protective effect of roselle on cardiac dysfunction in OB and OB+MI rats, which suggest its potential to be developed as a nutraceutical product for obese and obese patients with MI in the future.
Long-term nicotine intake is associated with an increased risk of myocardial damage and dysfunction. However, it remains unclear whether targeting mitochondrial reactive oxygen species (ROS) prevents nicotine-induced cardiac remodeling and dysfunction. This study investigated the effects of mitoTEMPO (a mitochondria-targeted antioxidant), and resveratrol (a sirtuin activator) , on nicotine-induced cardiac remodeling and dysfunction. Sprague–Dawley rats were administered 0.6 mg/kg nicotine daily with 0.7 mg/kg mitoTEMPO, 8 mg/kg resveratrol, or vehicle alone for 28 days. At the end of the study, rat hearts were collected to analyze the cardiac structure, mitochondrial ROS level, oxidative stress, and inflammation markers. A subset of rat hearts was perfused ex vivo to determine the cardiac function and myocardial susceptibility to ischemia–reperfusion injury. Nicotine administration significantly augmented mitochondrial ROS level, cardiomyocyte hypertrophy, fibrosis, and inflammation in rat hearts. Nicotine administration also induced left ventricular dysfunction, which was worsened by ischemia–reperfusion in isolated rat hearts. MitoTEMPO and resveratrol both significantly attenuated the adverse cardiac remodeling induced by nicotine, as well as the aggravation of postischemic ventricular dysfunction. Findings from this study show that targeting mitochondrial ROS with mitoTEMPO or resveratrol partially attenuates nicotine-induced cardiac remodeling and dysfunction.
The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells. Initially, compounds 8b and 8c exhibited strong inhibition on the production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50=12.01μM and 8c, IC50=4.86μM) and U937 (8b, IC50=3.44μM and 8c, IC50=1.65μM) cells. Placing vanillin at position Ar2 further improved the potency when both compounds 15a and 15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50=0.78μM and 15b, IC50=1.9μM while U937: 15a, IC50=0.95μM and 15b, IC50=0.92μM). Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the activity of downstream inflammatory COX-2 mediator. Finally, docking simulation on protein targets COX-2, IKK-β, ERK, JNK2, p38α and p38β were performed using the conformation of 15a determined by single-crystal XRD.
Gynura procumbens (Lour.) Merr. (GP) has been reported in previous studies to possess antihyperlipidaemic, antioxidative, and cardioprotective properties. This study was aimed to determine the effect of standardised 80% ethanol extract of GP on lipid profiles and oxidative status of hypercholesterolemic rats. Postmenopausal (PM) Sprague-Dawley rats were ovariectomised and fed with 2% cholesterol diet fortified with five times heated palm oil to develop hyperlipidaemia status. Two doses of the extract (250 and 500 mg/kg) and atorvastatin (10 mg/kg) were administered once daily via oral gavage for 24 weeks. Systolic blood pressure (SBP) was increased during the first month in the postmenopausal group and decreased with GP supplementation. Lipid droplets accumulation was shown at the tunica media (TM) area of the aorta in the postmenopausal group and reduced with GP supplementation. Total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and malondialdehyde (MDA) levels increased (p < 0.05) at 3 and 6 months in the postmenopausal group and were reduced with GP supplementation. GP also increased high-density lipoprotein (HDL) level in the postmenopausal group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were reduced in the postmenopausal group compared to control in the sham group but increased (p < 0.05) with GP supplementation. The results showed that the higher dose of GP (500 mg/kg) gave better effect. GP has the ability to reduce oxidative stress and prevent membrane cell damage through antioxidant enzyme activity modification and lipid profile changes in postmenopausal rats related to atherosclerosis.
The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.