A5085674779- Neuroinflammation and Neurodegeneration Mechanisms
- HIV Research and Treatment
- Analytical chemistry methods development
- Pesticide Residue Analysis and Safety
- Extracellular vesicles in disease
- Diet and metabolism studies
- Metabolomics and Mass Spectrometry Studies
- Sphingolipid Metabolism and Signaling
- HIV-related health complications and treatments
- Reproductive Physiology in Livestock
- Metabolism and Genetic Disorders
- Tryptophan and brain disorders
- Computational Drug Discovery Methods
- Ruminant Nutrition and Digestive Physiology
- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Fatty Acid Research and Health
- Immune cells in cancer
- Alzheimer's disease research and treatments
- Pharmacological Effects and Assays
- Adipose Tissue and Metabolism
- Analytical Methods in Pharmaceuticals
- Analytical Chemistry and Chromatography
- Adipokines, Inflammation, and Metabolic Diseases
- Lipid Membrane Structure and Behavior
Johns Hopkins University
2019-2024
Johns Hopkins Medicine
2019-2024
University of California, San Diego
2022
University of Central Florida
2017-2021
Indian Institute of Chemical Technology
2012-2014
There is a wide variety of extracellular vesicles (EVs) that differ in size and cargo composition. EVs isolated from human plasma or serum carry lipid, protein, RNA provides insights to the regulation normal physiological processes, pathological states. Specific populations have been proposed contain protein are biomarkers for neurologic systemic diseases. Although there considerable amount evidence circulating lipids multiple disease states, it not clear if these lipid enriched EVs,...
Abstract Schwann cell (SC)‐specific monocarboxylate transporter 1 (MCT1) knockout mice were generated by mating MCT1 f/f with myelin protein zero (P0)‐Cre mice. P0‐Cre +/− , have no detectable early developmental defects, but develop hypomyelination and reduced conduction velocity in sensory, not motor, peripheral nerves during maturation aging. Furthermore, mechanical sensitivity is evident aged deletion SCs impairs both their glycolytic mitochondrial functions, leading to altered lipid...
Background Alzheimer’s disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory persons with mild due to early AD and explores potential mechanisms action. Methods We conducted a 12-week, parallel-group, controlled feasibility trial ketogenic diet, modified Atkins diet (MAD), compared control patients impairments attributed AD....
Polypill is a fixed-dose combination that contains three or more active ingredients used as single daily pill to achieve large effect in preventing cardiovascular disease with minimal adverse effects. A novel and accurate liquid chromatography tandem mass spectrometry method using electrospray ionization mode has been developed validated for the simultaneous determination of amlodipine (AMD), valsartan (VAL) losartan (LOS) an internal standard (IS), hydrochlorothiazide (HCT) furosemide (FSD)...
Although HIV-1 Gag is known to drive viral assembly and budding, the precise mechanisms by which lipid composition of plasma membrane remodeled during are incompletely understood. Here, we provide evidence that sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) interacts with through hydrolysis creates ceramide necessary for proper formation envelope maturation. Inhibition or depletion nSMase2 resulted in production noninfectious virions incomplete lattices lacking condensed...
Abstract Background Cognitive decline in Alzheimer’s disease (AD) is associated with hyperphosphorylated tau (pTau) propagation between neurons along synaptically connected networks, part via extracellular vesicles (EVs). EV biogenesis triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2 (nSMase2)-mediated cleavage of sphingomyelin. We report, for first time, that human expression elevates brain ceramides and nSMase2 activity. Methods To determine...
Background: HIV infection results in immunometabolic reprogramming. While we are beginning to understand how this metabolic reprogramming regulates the immune response infection, do not currently impact of ART on immunometabolism people with (PWH). Methods: Serum obtained from HIV-infected (n = 278) and geographically matched seronegative control subjects 300) Rakai Uganda were used study. was before ~2 years following initiation individuals. We conducted metabolomics profiling serum focused...
Plant extracts are gaining more attention as therapeutic agents against inflammation. In this study, four different widely used herbals were selected, such holy basil leaf, sesame seed, long pepper, and cubeb pepper. We have evaluated the anti-inflammatory action of an aqueous extract from these herbs tested their effects on monocyte-derived macrophages (MDMs). MDMs pre-treated with individually for 2 h, followed by lipopolysaccharide (LPS) stimulation 24 h pro-inflammatory gene expression...
Abstract Background Triple-negative breast cancer (TNBC) is the most aggressive subtype and leads to poorest patient outcomes despite surgery chemotherapy treatment. Exploring new molecular mechanisms of TNBC that could lead development novel targets are critically important for improving therapeutic options treating TNBC. Methods We sought identify in by combining genomic functional studies with lipidomic analysis, which included mechanistic elucidate pathways tie lipid profile critical...
The discovery of novel biomarkers for peripartal diseases in dairy cows can improve our understanding normal and dysfunctional metabolism, lead to nutritional interventions that health milk production. Our objectives were characterize the plasma lipidome identify metabolites associated with common markers metabolic disease cattle. Multiparous Holstein (n = 27) enrolled 30 d prior expected parturition. Blood liver samples routinely collected through 14 postpartum. Untargeted lipidomics was...
Wilson disease (WD) is a metabolic disorder caused by inactivation of the copper-transporting ATPase 2 (ATP7B) and copper (Cu) overload in tissues. Excess Cu causes oxidative stress pathologic changes with poorly understood mechanistic connections. In Atp7b-/- mice established liver disease, activates stress-sensitive transcription factor Nrf2 (nuclear erythroid-derived 2-like 2). targets, especially sulfotransferase 1e1 (Sult1e1), are strongly induced cause elevation sulfated sterols,...
Combined antiretroviral therapy ushered an era of survivable HIV infection in which people living with (PLH) conduct normal life activities and enjoy measurably extended lifespans. However, despite viral control, PLH often experience a variety cognitive, emotional, physical phenotypes that diminish their quality life, including cognitive impairment, depression, sleep disruption. Recently, accumulating evidence has linked persistent CNS immune activation to the overproduction glutamate...
Extracellular vesicles (EVs) have been proposed to regulate the deposition of Aβ. Multiple publications shown that APP, amyloid processing enzymes and Aβ peptides are associated with EVs. However, very little is EVs compared total amount present in human plasma, CSF, or supernatants from cultured neurons. The involvement has largely inferred by pharmacological inhibition whole body deletion sphingomyelin hydrolase neutral sphingomyelinase-2 (nSMase2) a key regulator for biogenesis at-least...
Abstract Background Cognitive decline in Alzheimer’s disease (AD) is associated with prion-like tau propagation between neurons along synaptically connected networks, part via extracellular vesicles (EV). EV biogenesis triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2(nSMase2)-mediated cleavage of sphingomyelin. We report, for first time, that expression triggers an elevation brain ceramides and nSMase2 activity. Methods To determine therapeutic benefit...
Clinical and preclinical studies suggest that increases in long-chain ceramides blood may contribute to the development of depressive-like behavior. However, which factors these whether are sufficient induce behaviors is unclear. To begin address this issue, we examined effects high fat diet (HFD) short-term unpredictable (STU) stress on serum male female rats. We found brief exposure HFD or was selective concentrations ceramides, associated with depression people. Furthermore, combined...
To determine whether plasma eicosanoid levels are associated with immune, viral, and cognitive outcomes in people HIV (PWH).We measured 42 eicosanoids a longitudinal study of 95 PWH 25 demographically comparable uninfected participants. Routine clinical chemistry, virologic, immune markers, neuropsychological test battery assessing 7 domains were administered to all participants at 2 visits over an average 6.5 months.Plasma concentrations elevated (n = 95) compared seronegative controls 25)...
In this study, we tested the hypothesis that lipid peroxide-derived dicarboxylic acids (DCAs), by virtue of their ability to bind calcium (Ca), might be involved in atherosclerotic calcification. We determined azelaic acid (AzA) promote calcification human aortic smooth muscle cells (HASMCs), identified AzA calcified lesions, and compared its levels with control noncalcified lesions.