Theodoros Kelesidis's research while affiliated with University of California, Los Angeles and other places
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Publications (28)
No treatment exists for mitochondrial dysfunction, a contributor to end-organ disease in human immunodeficiency virus (HIV). The mitochondrial antioxidant mitoquinone mesylate (MitoQ) attenuates mitochondrial dysfunction in preclinical mouse models of various diseases but has not been used in HIV. We used a humanized murine model of chronic HIV inf...
The impact of tobacco cigarette (TCIG) smoking and electronic cigarette (ECIG) vaping on the risk of development of severe COVID-19 is controversial. The present study investigated levels of proteins important for SARS-CoV-2 pathogenesis present in plasma because of ectodomain shedding in smokers, ECIG vapers, and non-smokers (NSs). Protein levels...
Background:
Mitochondria regulate immune and organ function. It is unknown whether higher intracellular drug levels observed in peripheral blood mononuclear cells (PBMCs) treated with tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) may alter mitochondrial function and energy production in immune cells in HIV(+) patients...
Coronaviruses can cause serious respiratory tract infections and may also impact other end organs such as the central nervous system, the lung and the heart. The coronavirus disease 2019 (COVID-19) has had a devastating impact on humanity. Understanding the mechanisms that contribute to the pathogenesis of coronavirus infections, will set the found...
Atherosclerotic coronary artery disease (CAD) is the leading cause of mortality worldwide.¹ In this context, the burden of CAD shows considerable regional heterogeneity at the national level. For example, age-standardized mortality rates varied between 106 and 178 deaths per 100 000 at the level of German federal states in 2019.² The regional heter...
To date, there is no effective oral antiviral against SARS-CoV-2 that is also anti-inflammatory. Herein, we show that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has potent antiviral activity against SARS-CoV-2 and its variants of concern in vitro and in vivo . Mito-MES had nanomolar in vitro anti...
Abstract Background High-density lipoprotein (HDL) plays a critical role in protection against atherosclerosic and cardiovascular disease (ASCVD). In addition to contributing to clearing excess vascular cholesterol, HDL particles exhibit antioxidative functions, helping to attenuate adverse effects of oxidized low-density lipoproteins. However, the...
Novel therapeutic strategies are needed to attenuate increased systemic and gut inflammation that contribute to morbidity and mortality in chronic HIV infection despite potent antiretroviral therapy (ART). The goal of this study is to use preclinical models of chronic treated HIV to determine whether the antioxidant and anti-inflammatory apoA-I mim...
Introduction:
SARS-CoV-2, the virus responsible for the COVID-19 pandemic, gains entry into the host cell when its Spike protein is cleaved by host proteases TMPRSS2 and furin, thereby markedly increasing viral affinity for its receptor, angiotensin-converting enzyme-2(ACE2). In rodent and diseased human lungs, tobacco cigarette(TCIG) smoke increa...
Background
Despite advances in ART, people living with HIV (PLWH)continue to be at increased risk of cardiometabolic complications compared to HIV-uninfected individuals. Advanced glycation end products (AGEs) are implicated in the development and progression of cardiometabolic complications in the general population. Their role in HIV remains uncl...
Chronic inflammation, including among persons with HIV (PWH), elevates immune cell expression of lymphocyte activation gene 3 (LAG3); however, low plasma LAG3 predicts cardiovascular disease events in the general population. The associations among LAG3 plasma levels, subclinical atherosclerosis, inflammation, and HIV infection have not been well de...
Like tobacco cigarette (TCIG) smoking, long-term electronic cigarette (ECIG) vaping in young people is associated with elevated cellular oxidative stress (COS), which is important in the pathogenesis of many diseases, including atherosclerosis.¹ As with TCIG smoking,² even infrequent ECIG use may be associated with adverse biological effects with i...
Rationale: Chronic electronic cigarette (EC) users exhibit a higher susceptibility of low-density lipoprotein (LDL) to undergo oxidation as compared to non-user controls. However, there is a paucity of data regarding EC effects on lipid peroxidation in the blood and their relationship to cardiovascular risk.
Objective: To test the hypothesis that c...
Background:
The adipokines leptin and adiponectin, produced primarily by adipose tissue, have diverse endocrine and immunologic effects, and circulating levels reflect adipocyte lipid content, local inflammation, and tissue composition. We assessed relationships between changes in regional fat depots, leptin and adiponectin levels, and metabolic a...
It is unclear how oxidative stress triggered by smoking and vaping, may alter specific immune cell subsets. In this study, we showed that tobacco cigarette smoking, but not electronic-cigarette vaping, is associated with increased expression of major proteins in the TLR4- inflammasome-IL-6 signaling axis in monocyte subtypes and T cells. TLR4, sens...
The advent of highly sensitive molecular diagnostic techniques has improved our ability to detect viral pathogens leading to severe and often fatal infections that require admission to the Intensive Care Unit (ICU). Viral infections in the ICU have pleomorphic clinical presentations including pneumonia, acute respiratory distress syndrome, respirat...
Background
Tobacco cigarettes (TCs) increase oxidative stress and inflammation, both instigators of atherosclerotic cardiac disease. It is unknown if electronic cigarettes (ECs) also increase immune cell oxidative stress. We hypothesized an ordered, “dose‐response” relationship, with tobacco‐product type as “dose” (lowest in nonsmokers, intermediat...
SARS-CoV-2 infection is associated with significant lung and cardiac morbidity but there is a limited understanding of the endocrine manifestations of coronavirus disease 2019 (COVID-19). Although thyrotoxicosis due to subacute thyroiditis has been reported in COVID-19, it is unknown whether SARS-CoV-2 infection can also lead to decompensated hypot...
Neisseria gonorrhoeae is a rare cause of preseptal cellulitis, but infections can be severe. Rapid diagnosis is critical and can be expedited by nucleic acid amplification tests. Contact isolation precautions are encouraged for hospitalized patients with gonococcal preseptal cellulitis and a prolonged course of antibiotics is recommended.
Lorcaserin is a serotonin 2c receptor agonist, which promotes weight loss while improving type 2 diabetes and atherogenic lipid profile without higher rates of major cardiovascular events. The full spectrum of the possible lorcaserin‐induced cardiometabolic improvements remains to be clarified. Thus, we investigated how lorcaserin administration ma...
HIV-related cardiovascular disease (CVD) is a main cause of morbidity and mortality among HIV-infected persons, despite potent antiretroviral therapy (ART). However, the mechanisms of HIV-related CVD are unclear. Chronic HIV infection is a state of oxidative stress driven by several mediators including HIV per se, bacterial translocation, ART, mito...
Citations
... In addition, these animal models require a genetic variation of the cholesterol processing capacity, which is coupled with extreme changes in diet (e.g., Western-type diet) (Meir and Leitersdorf, 2004;Getz and Reardon, 2012). Moreover, different monocyte biology between humans and mice renders the study on the questions regarding macrophage foam cells to be more difficult (Hilgendorf and Swirski, 2012;Angelovich et al., 2017). ...
... Several pieces of evidence supported a possible relationship between GHD and COVID-19 severity and have also shed light on the potential beneficial effects of treatment with recombinant GH on COVID-19 patients [31]. In this regard, recently published articles showed that among the hormonal changes in long COVID patients are reduced GH levels and possibly reduced insulin/IGF-1 signaling [34,35]. Considering all the above, a close relationship between ferritin metabolism, obesity, hepatic steatosis, and the GH/IGF-1 axis with COVID-19 severity is conceivable. ...
... Given the findings that mtROS is significantly increased compared to extracellular ROS [44], a targeted approach to bringing ROS levels back to normal would be beneficial and hence further studies with mitochondrial antioxidants on infected cells are required. Recent studies exploited other mitochondrially targeted antioxidants like mitoquinone/mitoquinol mesylate (Mito-MES), which showed significant antiviral activity against SARS-CoV-2 and lower viral titre by nearly 4 log units which led to reduced hyper-inflammation in the host as well [130]. Not only might these antioxidants show positive signs as therapeutics, they might also provide greater insight into the role mtROS plays in assisting SARS-CoV-2 infection of host cells. ...
... Briefly, a traditional lipid panel (HDL-c, estimated LDL-c, and triglyceride levels) and measures of glucoregulation (glycemia, insulinemia, HOMA-IR, and HbA1c) were determined by CLIA-certified clinical laboratories (Meriter Labs, Madison, WI and ARUP, Salt Lake City, UT). Oxidized HDL (oxHDL) levels were determined by measuring lipid peroxidation of HDL (23). Plasma fibrinogen and high sensitive C reactive protein (CRP) levels were measured using a BNII nephelometer (Dade Behring Inc., Deerfield, IL). ...
... All participants had refrained from smoking 12 h before the study session. Healthy male and female volunteers with previously described characteristics [11] between the ages of 21 years and 45 years were eligible for enrollment if they were chronic (> 1 year), as follows: (1) active TCIG smokers (regardless of the number of pack-years) or (2) ECIG vapers (no dual users) or (3) non-smokers. Former TCIG smokers were eligible to be included in the nonsmoker group, if greater than 1 year had elapsed since quitting. ...
... The reason for the decrease of sLAG3 in patients with CAD is still unknown. Many factors such as race, and inflammatory factors may influence the sLAG3 level (25, 45). Besides, LAG3 expression may be also regulated by methylation, T cell receptor pathway activation, cytokines, and metalloproteinase (46). ...
... However, the nicotine concentration in e-liquid has shown to be inconsistent to labeling (Girvalaki et al., 2020), and even e-cigarettes marketed as containing 0% nicotine have been found to contain nicotine (Goniewicz et al., 2015). Contrary to what young people may assume, e-cigarette aerosol is not harmless (Kelesidis et al., 2021;Center for Disease Control and Prevention, 2021;U.S. Department of Health and Human Services, 2016). ...
... CBs leachate appeared to modulate also lipid metabolism in mussels PCTS by the downregulation of acox1. The impairment of fatty acid metabolism has already been observed in different mammalian organs and cell types, with reduced activity of β-oxidation enzymes and increased lipid accumulation after in vivo and in vitro exposure to cigarette smoke or extracts (Gong et al., 2019;Gupta et al., 2021); conversely, other studies reported an increase of the same enzymes, reflecting the high complexity of cigarette butts toxicity on fatty acid metabolism (Li et al., 2021). The low levels of PAHs, measured in CB leachates in this study may account for the lack of transcriptional regulation of cyp3a1, which is not strongly regulated by Ah receptor particularly in invertebrates, but known to be responsive to such chemicals in mussels digestive gland (Cubero-Leon et al., 2012;Giuliani et al., 2013). ...
... Data from the ACTG A5260s and ADVANCE trials indicate that ART-associated weight gain results in greater increases in fat mass including visceral adipose tissue than in lean mass, with women experiencing significantly greater increases in fat mass than men [33,34]. Weight gain after starting ART is associated with an increase in leptin but not adiponectin [49], insulin resistance [50], and with an increased risk of diabetes across all BMI strata [51,52]. A recent NA-ACCORD analysis found a (non-significant) 17% increased risk of incident diabetes with INSTI versus NNRTI which was no longer present when accounting for 12-month weight gain [53]. ...
... FDG, 18 F-fluorodeoxyglucose; SUV max , standardized uptake value. in this study. However, in prior studies using the highly sensitive methodology including flow cytometry with fluorescent probes in otherwise healthy young people, we have previously reported differences in oxidative stress and inflammation among the three cohorts (Gupta et al., 2021;Kelesidis et al., 2020Kelesidis et al., , 2021aKelesidis et al., , 2021b. Although, in this report using PET/CT, we did not find differences among nonsmokers, e-cigarette users, and tobacco users in inflammation in the splenocardiac axis, we feel it is best for this investigation to be replicated by other investigators. ...