Sameh S Ali

University of California, San Diego | UCSD · Department of Medicine

Background COVID-19 severity and high in-hospital mortality are often associated with severe hypoxemia, hyperlactatemia, and acidosis. Since neutrophil numbers in severe COVID-19 can exceed 80% of the total circulating leukocytes and that they are massively recruited to infected lungs, we investigated whether metabolic acidosis mediated by the glyc...

Roles of platelets during infections surpass the classical thrombus function and are now known to modulate innate immune cells. Leukocyte-platelet aggregations and activation-induced secretome are among factors recently gaining interest but little is known about their interplay with severity and mortality during the course of SARS-Cov-2 infection....

Increased oxidative stress underlies a variety of diseases, including diabetes. Here we show that the cobalamin/vitamin B12 analog cobinamide is a strong and multi-faceted antioxidant, neutralizing superoxide, hydrogen peroxide, and peroxynitrite, with apparent rate constants of 1.9 × 108, 3.7 × 104, and 6.3 × 106 M−1 s−1, respectively for cobinami...

Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median...

Hydroxyl radical (• OH) scavenging capacity of aqueous dill (Anethum graveolens L.) shoot (ADSh) extract was assessed using electron paramagnetic resonance (EPR) spectroscopy. ADSh extract (at concentrations of 0.5 and 10 mg/ml) exerted high (OH) radical scavenging power. ADSh extract was further fractionated on Diaion HP20 column to yield five fra...

Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 25 patients who were followed up for a median...

Introduction Incidents of myocardial infarction and sudden cardiac arrest vary with time of the day, but the mechanism for this effect is not clear. We hypothesized that diurnal changes in the ability of cardiac mitochondria to control calcium homeostasis dictate vulnerability to cardiovascular events. Objectives Here we investigate mitochondrial...

Mitochondrial and immune dysfunctions are often implicated in the aetiology of autism spectrum disorder (ASD). Here, we studied for the first time the relationship between ASD severity measures and mitochondrial respiratory rates in freshly isolated platelets as well as the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NO...

Liver malignant growth incorporates hepatocellular carcinoma (HCC) involving 75%-85% of liver patients respectively which is attributed mainly to the lack of early biomarker/s and poor accesses to affordable, simple diagnostic techniques, which is not available in the conventional techniques of HCC diagnosis. Consequently, there is an urgent need t...

In the present work, antioxidant activity, total phenolics (TP), and total flavonoids (TF) contents of aqueous and methanol extracts of celery were determined, in addition to untargeted metabolites profiling its methanol celery root extract (MCRE) via UPLC‐MS. Although MCRE exhibited the lowest TPC and TFC levels, it presented the most potential hy...

Synaptosomal membrane peroxidation and alteration in its biophysical properties are associated with Aluminium (Al) toxicity that may lead to cognitive dysfunction and Alzheimer’s disease (AD) like pathogenesis. Here we investigated the therapeutic potential of Lepedium sativum (LS) as a natural anti-inflammatory, antioxidant and as acetyl cholinest...

Reprogramming autologous adult cells to pluripotent cells allows for relatively safe cell replacement therapy. This can be achieved by nuclear transfer, cell fusion, or induced pluripotent stem cell technology However, the epigenetic memory of the cell is considered as a great challenge facing the complete reprograming of cells by these methods. In...

A trend of higher NOX-mediated superoxide yield in isolated synaptosomes from Al-treated rat brains as determined by EPR spin-trapping spectroscopy. (A) Representative EPR spectra evolved over 20 min from NADPH stimulation of NOX in AD (red) or control (black) synaptosomes in the presence of DMPO spin trap. The boxed peaks are parts of signals that...

Triple-negative breast cancer (TNBC) subtype is among the most aggressive cancers with the worst prognosis and least therapeutic targetability while being more likely to spread and recur. Cancer transformations profoundly alter cellular metabolism by increasing glucose consumption via glycolysis to support tumorigenesis. Here we confirm that relati...

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unif...

I n this work we have investigated the alterations in membrane physical properties and peroxidation mediated by AlCl3 in isolated synaptosomes of rat cortical brain tissue after 21, 42 and 65 days. The potential therapeutic role of Lepedium sativum (LS) as a natural anti-inflammatory, antioxidant and as acetylcholinesterase inhibitor in treating AD...

[This corrects the article DOI: 10.1155/2016/1089364.].

The prevalence of both Alzheimer’s disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes,...

The aim of this study is to compare human bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs), for their differentiation potentials to form insulin-producing cells. BM-MSCs were obtained during elective orthotopic surgery and AT-MSCs from fatty aspirates during elective cosmetics procedur...

A series of novel quinones was synthesized by reacting tetrabromo-p-benzoquinone with amino oligo(ethylene glycol) dendrons of generation numbers g = 0–2. According to the performed shake-flask experiments, their aqueous solubility (S = 18 mg l−1–1.6 g ml−1) and partition coefficients (logPoct/wat = 2.53–0.21) can be tuned in a wide range as a func...

Pathophysiology of chronic kidney disease (CKD) is driven by alterations in surviving nephrons to sustain renal function with ongoing nephron loss. Oxygen supply-demand mismatch, due to hemodynamic adaptations, with resultant hypoxia, plays an important role in the pathophysiology in early CKD. We sought to investigate the underlying mechanisms of...

We report a family of novel microporous polymers constructed through covalent cross linkage of the buckyball and linear dialkyne through Cu-mediated, one-pot synthesis. A novel functionalization-polymerization pathway is described whereby Cu-mediated free radical species, generated in-situ, triggered multiple additions of the ditopic alkyne to C60....

Sex-specific differences in mitochondrial function and free radical homeostasis are reported in the context of aging but not well-established in pathogeneses occurring early in life. Here, we examine if sex disparity in mitochondria function, morphology, and redox status starts early and hence can be implicated in sexual dimorphism in cardiac as we...

Bardoxolone-methyl (BAR) is reported to have anti-inflammatory, anti-proliferative and anti-fibrotic effects. BAR activates Nrf2 and may ameliorate oxidative stress through induction of antioxidant genes, but also inhibits NFkB. However, off-target effects, probably concentration-dependent, have limited the clinical use of BAR. Nrf2 regulates expre...

Table (1): The cells from both sources were strongly positive for the MSCs surface markers: CD73, CD90 and CD105 and were negative for the hematopoietic stem cell markers; CD14, CD 34 and CD 45. Table (2): By immunofluorescence, the proportion of insulin-positive cells at the end of differentiation ranged between1.0–5% for BM-MSCs and between 1.0–...

Hydrogen sulfide is a highly toxic gas-second only to carbon monoxide as a cause of inhalational deaths. Its mechanism of toxicity is only partially known, and no specific therapy exists for sulfide poisoning. We show in several cell types, including human inducible pluripotent stem cell (hiPSC)-derived neurons, that sulfide inhibited complex IV of...

Reactive oxygen and nitrogen species (ROS and RNS) play crucial roles in triggering, mediating, and regulating physiological and pathophysiological signal transduction pathways within the cell. Within the cell, ROS efflux is firmly controlled both spatially and temporally, making the study of ROS dynamics a challenging task. Different approaches ha...

Disruption of cellular redox homeostasis is implicated in a wide variety of pathologic conditions and aging. A fundamental factor that dictates such balance is the ratio between mitochondria-mediated complete oxygen reduction into water and incomplete reduction into superoxide radical by mitochondria and NADPH oxidase (NOX) enzymatic activity. Here...

Results from previous investigations have indicated that glucose-stimulated insulin secretion (GSIS) is affected by changes in cholesterol and its intermediates, but the precise link between secretion and cholesterol has not been thoroughly investigated. In this study, we show the contribution of both protein isoprenylation and cholesterol-dependen...

Traumatic brain injury (TBI) enhances pro-inflammatory responses, neuronal loss and long-term behavioral deficits. Caveolins (Cavs) are regulators of neuronal and glial survival signaling. Previously we showed that astrocyte and microglial activation is increased in Cav-1 knock-out (KO) mice and that Cav-1 and Cav-3 modulate microglial morphology....

Reactive oxygen species (ROS) are common cellular and intracellular messengers that can also act deleteriously to exacerbate a wide variety of pathophysiologies. In particular, deleterious ROS generation can directly damage proteins and DNA, among other cellular targets, and improper ROS generation has been implicated as a key signal in ischemia-re...

Diabetic microvascular complications have been considered to be mediated by a glucose-driven increase in mitochondrial superoxide anion production. Here, we report that superoxide production was reduced in the kidneys of a steptozotocin-induced mouse model of type 1 diabetes, as assessed by in vivo real-time transcutaneous fluorescence, confocal mi...

Scope: The flavanol (-)-epicatechin (Epi), a component of cacao, has cardiac protective benefits in humans. Our previous study demonstrated Epi has δ-opioid receptor (DOR) binding activity and promotes cardiac protection. Here we examined the effects of 10 days of Epi treatment on: cardiac mitochondrial respiration, reactive oxygen species product...

Diabetes is a worldwide epidemic with cardiovascular disease being a major complication. Caveolins act as scaffolding molecules for regulating signaling. Overexpression of caveolin protects the heart from cardiovascular stress. We hypothesize that cardiac‐specific caveolin‐3 (Cav‐3) overexpression (OE) will protect the diabetic heart. Transgene neg...

Results from previous investigations have indicated that glucose-stimulated insulin secretion (GSIS) is affected by changes in cholesterol and its intermediates, but the precise link between secretion and cholesterol has not been thoroughly investigated. In this study, we show the contribution of both protein isoprenylation and cholesterol-dependen...

Significance Early signaling events leading to protection in the heart under cardiac injury are poorly understood. We identified one such protein, A kinase interacting protein (AKIP1), as a modulator that responds to oxidative stress; up-regulation of AKIP1 showed protection to ischemic injury through enhanced mitochondrial integrity. We show AKIP1...

We show here that the apposition of plasmamembrane caveolae and mitochondria (first noted in electron micrographs >50 yr ago) and caveolae-mitochondria interaction regulates adaptation to cellular stress by modulating the structure and function of mitochondria. In C57Bl/6 mice engineered to overexpress caveolin specifically in cardiac myocytes (Cav...

Copper transporter 1 (CTR1) is the major copper (Cu) influx transporter in mammalian cells. We report here that CTR1 is required for the activation of signaling to the MAPK pathway by the ligands of three major receptor tyrosine kinases (RTK) including FGF, PDGF and EGF. Induction of Erk1/2 phosphorylation was compared in isogenic wild type CTR1(+/...

Through long-term laboratory selection, we have generated a Drosophila melanogaster population that tolerates severe, normally lethal, level of hypoxia. This strain lives perpetually under severe hypoxic conditions (4% O(2)). In order to shed light on the mechanisms involved in this adaptation, we studied the respiratory function of isolated mitoch...

Epicatechin, a dark chocolate flavonol/antioxidant, is linked to cardiovascular cytoprotection. Myocardial infarct size was decreased in epicatechin‐treated mice compared to controls, and this effect was blocked by a DOR antagonist. Low‐dose epicatechin, with little antioxidant activity, is protective; however, the mechanism of this cytoprotection...

Circadian variations in pro‐ and antioxidants, enzymes, and markers of oxidative stress such as malonedialdehyde have been reported. However, nothing is known about the source(s) of free radicals that trigger or modulate these periodic variations. Here we explore the sources and levels of Reactive Oxygen Species (ROS) in young animal brains. We emp...

Cobinamide, a vitamin B12 precursor, has a high affinity for cyanide and is an effective antidote for cyanide poisoning in animal models. However, when given as an intramuscular injection at high concentrations, the compound forms aggregates that both inhibit its absorption and damage the muscle tissue. The objective of this study is to investigate...

The aged heart is more susceptible to injury with limited understanding of the cause. We have shown that caveolin‐3 (Cav‐ 3, a heart scaffolding protein) is critical to cardiac protection. Cav‐ 3 protein is 50% reduced in 2 year old hearts. Cardiac myocytespecific overexpression of Cav‐3 (Cav‐3 OE) increased Cav‐3 expression through 2 years of age...

The production of Reactive Oxygen Species (ROS) leads to neurodegeneration in Meth abusers. We examined the contribution of ROS from non‐neuronal cells that affect local immunity and neuron survival in the brain. Using astrocyte (C8S), microglia (BV2) and macrophage (THP1) cell lines we show direct and differential effects of Meth on ROS pathways....

The currently accepted scheme for reactive oxygen species production during ischemia/reperfusion injury is characterized by a deleterious mitochondria-derived burst of radical generation during reperfusion; however, recent examination of the penumbra suggests a central role for NADPH-oxidase (Nox)-mediated radical generation during the ischemic per...

Prolonged hyperoxia exposure generates excessive reactive oxygen species (ROS) and potentially leads to oxidative injury in every organ. We have previously generated Drosophila melanogaster flies that tolerate extreme oxidative stress (90%-95% O₂), a lethal condition to naive flies, through a long-term laboratory selection. We found that hyperoxia-...

Decreased expression of prosurvival and progrowth-stimulatory pathways, in addition to an environment that inhibits neuronal growth, contribute to the limited regenerative capacity in the central nervous system following injury or neurodegeneration. Membrane/lipid rafts, plasmalemmal microdomains enriched in cholesterol, sphingolipids, and the prot...

Volatile anesthetics have a dual effect on cell survival dependent on caveolin expression. The effect of volatile anesthetics on cancer cell survival and death after anesthetic exposure has not been well investigated. The authors examined the effects of isoflurane exposure on apoptosis and its regulation by caveolin-1 (Cav-1). The authors exposed h...

Decreased expression of prosurvival and progrowth-stimulatory pathways, in addition to an environment that inhibits neuronal growth, contribute to the limited regenerative capacity in the central nervous system following injury or neurodegeneration. Membrane/lipid rafts, plasmalemmal microdomains enriched in cholesterol, sphingolipids, and the prot...

We hypothesized that cardiac myocyte-specific overexpression of caveolin-3 (Cav-3), a muscle-specific caveolin, would alter natriuretic peptide signaling and attenuate cardiac hypertrophy. Natriuretic peptides modulate cardiac hypertrophy and are potential therapeutic options for patients with heart failure. Caveolae, microdomains in the plasma mem...

Microglia are ramified cells serving as central nervous system (CNS) guardians. Following CNS injury or infection, microglia contract and cells adopts an amoeboid morphology capable of proliferation and migration. Though extracellular factors may be involved in this transformation, the control point for microglia activation or repression is unknown...

The aged brain exhibits a loss in gray matter and a decrease in spines and synaptic densities that may represent a sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR), discrete regions of the plasmalemma enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for the development and stabiliza...

Unregulated production of reactive oxygen species (ROS) is a marker of cellular and organismal aging linked to cognitive decline in humans and rodents. The sources of elevated ROS contributing to cognitive decline are unknown. Because NADPH oxidase (Nox) inhibition may prevent memory decline with age, we hypothesized that Nox and not mitochondrial...

Temperature (T) reduction increases lifespan, but the mechanisms are not understood. Because reactive oxygen species (ROS) contribute to aging, we hypothesized that lowering T might decrease mitochondrial ROS production. We measured respiratory response and ROS production in isolated mitochondria at 32, 35, and 37 °C. Lowering T decreased the rates...

Breathing-disordered states, such as in obstructive sleep apnea, which are cyclical in nature, have been postulated to induce neurocognitive morbidity in both pediatric and adult populations. The oscillatory nature of intermittent hypoxia, especially when chronic, may mimic the paradigm of ischemia-reperfusion in that tissues and cells are exposed...

Superoxide imaging in IL-6-/- brain. Superoxide levels are substantially lower in the hippocampal CA1 and cortex regions of IL-6-/- mouse. Confocal images were acquired as described for Figure 2a. (10.58 MB TIF)

Synaptosomal mitochondria. Synaptosomal mitochondrial respiration is not affected by age or IL-6 treatment. State 3 respiration was initiated by malate plus pyruvate (10 mM each) (ADP already present), state 4 respiration was measured after addition of the F0F1-ATPase inhibitor, oligomycin, and maximal respiration was measured after adding the unco...

PV-interneurons in PFC. A statistically significant decrease in PV-positive cell counts was observed in the prelimbic region of prefrontal cortex (PFC). The region analyzed is shown at left. Values are mean±SEM, P = 0.007 by t-test. (10.03 MB TIF)

Background: Multiple studies have shown that plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) are elevated in patients with important and prevalent adverse health conditions, including atherosclerosis, diabetes, obesity, obstructive sleep apnea, hypertension, and frailty. Higher plasma levels of IL-6, in turn, increase the risk...

Hypoxic-ischemic brain injury (stroke) continues to be the third leading cause of death in the USA. Hypoxia in the absence of ischemia, such as that occurs in individuals with sleep apnea, chronic obstructive pulmonary disease, and a number of other conditions, also represents a major and growing health issue. A great deal has been learned about th...

Adult exposure to NMDA receptor antagonists, such as ketamine, produces psychosis in humans, and exacerbates symptoms in schizophrenic patients. We recently showed that ketamine activates the innate immune enzyme NADPH-oxidase in brain, and that the superoxide produced leads to dysfunction of a subset of fast-spiking inhibitory interneurons express...

Superoxide radical anion is a biologically important oxidant that has been linked to tissue injury and inflammation in several diseases. Here we carried out a structure-activity study on six different carboxyfullerene superoxide dismutase (SOD) mimetics with distinct electronic and biophysical characteristics. Neurotoxicity via N-methyl-D-aspartate...

Vitamin E is the major lipid-soluble chain-breaking antioxidant in mammals and plays an important role in normal development and physiology. Deficiency (whether dietary or genetic) results in primarily nervous system pathology, including cerebellar neurodegeneration and progressive ataxia (abnormal gait). However, despite the widely acknowledged an...

In lower organisms, such as Caenorhabditis elegans and Drosophila, many genes identified as key regulators of aging are involved in either detoxification of reactive oxygen species or the cellular response to oxidatively-damaged macromolecules. Transgenic mice have been generated to study these genes in mammalian aging, but have not in general exhi...

Abuse of the dissociative anesthetic ketamine can lead to a syndrome indistinguishable from schizophrenia. In animals, repetitive exposure to this N-methyl-d-aspartate–receptor antagonist induces the dysfunction of a subset of cortical fast-spiking inhibitory interneurons, with loss of expression of parvalbumin and the γ-aminobutyric acid–producing...

Photophysical properties in dilute acetonitrile solution are reported for a number of iridium(III) and rhenium(I) complexes. The nature of the lowest excited state of the complexes under investigation is either metal-to-ligand charge transfer ((3)MLCT) or a ligand centred ((3)LC) state. Rate constants, k(q), for quenching of the lowest excited stat...

Mitochondrial oxidation of fuel generates an electrochemical gradient via outward pumping of protons by the electron transport chain. ATP production via ATP synthase is then facilitated by the inward flux of protons down the gradient. However, during the 1970s, David Nicholls and colleagues found that the electrochemical gradient could be uncoupled...

Gender is a profound determinant of aging and lifespan, but little is known about gender differences in free radical homeostasis. Free radicals are proposed as key elements in the multifactorial process of aging and it is predicted that the longer-lived gender should have lower levels of oxidative stress. While the majority of studies on aging have...

The absorption and fluorescence spectra of 2‐(p‐dimethylaminostyryl)benzoxazole, DMASBO, and its benzothiazole analogue, DMASBT, have been studied in different solvents and at various acid concentrations. Two types of monocation are formed simultaneously in all solvents at relatively lower acid concentrations. The neutral DMASBO and DMASBT as well...

Superoxide, a potentially toxic by-product of cellular metabolism, may contribute to tissue injury in many types of human disease. Here we show that a tris-malonic acid derivative of the fullerene C60 molecule (C3) is capable of removing the biologically important superoxide radical with a rate constant (k(C3)) of 2 x 10(6) mol(-1) s(-1), approxima...

The photo-induced electron-transfer reaction of 4,4-bipyridine (BPY) with triethylamine (TEA) in acetonitrile is studied by laser flash photolysis. The reaction mechanism and kinetics are found very sensitive to the presence of a small amount of water. At low water concentrations (i.e. <0.003 M), an extremely fast-rising metastable product is detec...